Dr. Onishi is the head scientist of a secret government psychic research project and also serves as the scientific advisor to the Colonel, the military leader overseeing the project. He represents the second generation of scientists to manage the research, having taken over after the original team was killed by the psychic child Akira. His defining trait is an overwhelming scientific curiosity that completely overshadows any ethical concerns for the well-being of his test subjects. This negligence directly leads to the awakening and nurturing of Tetsuo's dangerous destructive powers.

Throughout the story, Dr. Onishi is motivated by a singular, obsessive goal to understand and replicate the god-like psychic abilities that caused the destruction of Tokyo. After investigating Tetsuo, he discovers the young biker possesses power similar to Akira's and, with the Colonel's permission, begins a series of experiments intended to cultivate a new psychic weapon. The Colonel, fearing another catastrophe, explicitly warns the doctor to terminate Tetsuo immediately if it appears his power is growing beyond control. Dr. Onishi disregards this direct order, driven by the hope that studying Tetsuo will finally solve the mystery surrounding the nature of Akira's immense power. He is less a malicious villain and more a personification of unrestrained, amoral research, someone who is eager to push the boundaries of human evolution without considering the consequences.

His key relationship is with the Colonel, to whom he acts as an advisor, though their partnership is strained by their conflicting goals: the Colonel prioritizes control and security, while Dr. Onishi prioritizes knowledge and discovery at any cost. He also has a direct and exploitative relationship with Tetsuo, viewing him not as a person but as the key to unlocking the secrets of psychic power. His role in the story is that of a catalyst; his decision to experiment on Tetsuo unlocks the boy's potential, setting the final acts of the narrative into motion. He is present as a detached observer when Akira is reawakened, analyzing the event through his instruments and comparing it to the birth of a new universe. Dr. Onishi meets his end not through direct combat, but when the vehicle he is inside is crushed and destroyed during the colossal psychic upheaval that consumes Neo-Tokyo. His notable abilities lie not in combat, but in his scientific expertise and access to advanced technology, such as psychic monitoring equipment including the Saturn capsule used to test Tetsuo's telekinetic levels.