Meisuke Nueno, better known by his nickname Nube, is the main protagonist of his story. He is a twenty-five-year-old man who serves as the homeroom teacher for class 5-3 at Domori Elementary School. Unbeknownst to most of his students and colleagues, he is also one of Japan's most powerful exorcists, a calling he pursues to protect the innocent from the many ghosts and demons, known as yokai, that inhabit the world. The black glove he always wears on his left hand conceals his greatest weapon and burden: the Oni no Te, or Demon Hand.

Nube's background is marked by tragedy and sacrifice, which directly shapes his adult life and choices. As a child, he possessed strong spiritual energy but lacked the ability to control it, making him a frequent target for possession by evil spirits and leading to bullying from his peers. He was saved and guided by his own elementary school teacher, a kind woman named Minako, who risked her life to exorcise the spirits within him. This act of selfless courage left a profound impression on young Meisuke, planting the seeds for his future career. Another pivotal tragedy occurred within his family. His father, also an exorcist, initially helped people for free out of the goodness of his heart. When Nube's mother fell ill, the people his father had previously aided refused to return the favor, leaving the family with no money for medicine. After his mother's death, Nube's father became embittered and abandoned his son, reinventing himself as a wealthy, money-driven spiritualist named Mugenkai Jikuu. This betrayal left Nube with a deep-seated aversion to using his spiritual powers for personal financial gain. The tragic cycle concluded when Nube became a teacher himself. An immensely powerful oni possessed one of his students, and in the ensuing battle, the spirit of his mentor, Minako, sacrificed herself to help Nube seal the demon within his own left hand. The resulting Oni no Te is a monstrous appendage that replaces his hand, and Minako's spirit remains within it, helping to restrain the demon's power.

Nube's personality is a striking and endearing contrast between his professional life and his private struggles. As a teacher and exorcist, he is defined by an unshakable sense of responsibility and a fierce, protective love for his students. His most common catchphrase and guiding principle is a declaration to protect his class. He faces terrifying supernatural entities with immense bravery, often risking his life to ensure the safety of the children in his care. On a typical school day, however, he is a cheerful, goofy, and slightly eccentric figure who is not above clowning around to make his students laugh. This lighthearted exterior masks a life of profound poverty. Nube stubbornly refuses to charge for his exorcism work and spends his modest teacher's salary recklessly on pachinko (a pinball game) and treating his students to meals. As a result, he is perpetually broke, often reduced to eating his students' leftovers or surviving on instant noodles in the days leading up to his paycheck. He lives in a run-down apartment and has been known to sleep at school for the better amenities. He also has a comical weakness for beautiful women, frequently chasing after attractive female colleagues like Ritsuko Takahashi, though these pursuits are almost never successful.

Within the story, Nube's primary role is as the protector and mentor of his fifth-grade class. The narrative typically follows one of his students who stumbles upon a supernatural phenomenon, and Nube steps in to resolve the crisis, often turning the experience into a lesson about courage, empathy, or responsibility. His key relationships are central to the plot. He shares a deep, unspoken bond with his fellow teacher, Ritsuko Takahashi, for whom he harbors a crush. However, his most significant romantic relationship is with Yukime, a snow woman yokai he saved years ago. What begins as an unusual friendship eventually blossoms into deep love, and the two marry later in the manga's continuity. He has a complex rivalry with the powerful and mischievous nine-tailed fox spirit, Tamamo, who often causes trouble but occasionally becomes an ally. His most painful relationship is with his estranged father, Jiku, a rift that only begins to heal after many years. Among his students, he has close ties with the core members of class 5-3, including the brave but impulsive Hiroshi Tateno and his childhood friend, the tomboyish Kyoko Inaba.

Throughout the series, Nube undergoes significant development. He learns to better control the Oni no Te and masters new spiritual techniques. He confronts the trauma of his past, ultimately reconciling with his father. His character arc moves from a man who is somewhat oblivious to matters of the heart to one who finds true love and builds a family with Yukime. In later sequel series, such as Jigoku Sensei Nube Neo, he is depicted as an older, still-poor teacher who, after temporarily losing his powers, must undertake new training to master a more powerful and dangerous technique called Oni no Te Neo.

Nube's notable abilities are vast, stemming from his own spiritual power, the Oni no Te, and a collection of holy tools. The Oni no Te is his primary weapon, allowing him to exorcise demons, communicate with spirits, and perform powerful attacks that manifest as massive, spectral hands. He possesses the Sutra of the White-Robed Goddess, a scroll of paper that can be used like a whip or a chain to bind and seal evil spirits. He has a crystal ball that can reveal invisible ghosts and replay past spiritual events, and a set of prayer beads used for various rituals. Nube can also perform the Youshin Jutsu, a technique that allows him to separate his spiritual essence from his body, often taking the form of his younger self, to investigate cases discreetly. In later continuities, his power evolves further, demonstrating his ongoing growth as a protector who will go to any length to defend his students.