Karen Kisaragi is a central character in the anime and light novel series Hundred, primarily known as the younger sister of the protagonist, Hayato Kisaragi. Her early life has been significantly marked by illness, spending much of her childhood in the hospital while her brother began his training at Little Garden Academy. This frail health is the very reason Hayato decided to become a Slayer, in order to secure the funds for her first-class medical treatment. Orphaned along with her brother during the Second Attack, the siblings were eventually taken back to Yamato where they lived in an orphanage.

At her core, Karen is characterized by a gentle and sweet personality, but this is underpinned by an intense and deeply protective attachment to her brother. She possesses a strong brother complex, becoming extremely jealous and wary whenever other girls show any interest in or try to get close to Hayato. Despite this often-manifesting possessiveness, she is not inherently hostile, and her shy, determined nature becomes more confident as she pursues her own path. A key turning point in her life is her deep admiration for the world-famous singer Sakura Kirishima. After hearing Sakura sing, Karen develops a passion for music, and this eventually leads her to debut as an idol herself, using her unique abilities for performances. She looks up to Sakura as a role model and big sister, though this friendship does not exempt Sakura from Karen's jealousy if she gets too friendly with Hayato.

Karen's role in the story evolves from a bedridden patient to an active participant in the world of Slayers. Driven by her desire to stay by her brother's side and inspired by her idol, she enrolls as a second-year student at Little Garden Middle School. As her talent is discovered, she begins training and working as an idol, becoming a popular performer known on stage as the Little Little Witch. Her determination and willpower are central to her character, pushing her to overcome her physical limitations to become both a warrior and an entertainer. In the narrative's later progression, she advances to her third year, and fifteen years after the main events, she retires from being an idol but continues her career as a regular singer, showing her lasting passion for music.

In terms of her abilities, Karen possesses a unique type of Hundred known as the Miracle Holy Charm, also referred to as Divine Card. This is a Fortune Hundred that manifests as a set of tarot-like cards. Rather than having a fixed form, the cards orbit around her and automatically transform into the most suitable weapon or equipment based on her desires and the situation at hand, granting her great versatility in both combat and performance. During her time in the hospital, she also developed a keen interest in the occult, often using tarot cards for fortune-telling with an almost clairvoyant hit rate, a skill she frequently applies to predict events in her brother's social life.