Kotaro Yanagisawa, initially operating under the alias Shiro, is a central antagonist whose research forms the basis of the series. He was a brilliant biologist from a wealthy family who took over the struggling Yukimura Pharmaceutical company and entered an arranged relationship with its heiress, Aguri Yukimura. As a scientist, he was completely amoral, driven solely by his work to create anti-matter within a living host. To achieve this, he acquired the imprisoned assassin known as the God of Death as his test subject and assigned Aguri to observe the prisoner, seeing her as entirely expendable. The experiment succeeded, but a related test on the moon caused a catastrophic explosion that destroyed seventy percent of its mass. Fearing his test subject would suffer the same fate, Yanagisawa ordered his termination. Aguri, however, warned the prisoner, triggering his transformation into a tentacled being and his violent escape. Yanagisawa survived the ensuing lab explosion but lost his left eye, forcing him to rely on a mechanical prosthetic. Aguri was killed in the incident, and the failure of his project along with her death deeply wounded his pride.

Yanagisawa is defined by arrogance, a complete absence of ethics, and a manipulative, abusive nature. He views everyone around him as disposable tools for his own ends. His primary motivation is vengeance against Koro-sensei, the being created from his experiment, whom he blames for destroying his life and his legacy. In the story, he operates in secret to orchestrate attacks on Koro-sensei. He finds a deeply troubled orphan, Itona Horibe, and implants him with tentacles to act as a weapon. After Itona fails repeatedly, Yanagisawa coldly discards him. He also has a connection to Aguri’s younger sister, Kaede Kayano, whom he allows to infiltrate Koro-sensei’s class using his technology, viewing her as a capable but still expendable asset. His relationships are entirely transactional and defined by manipulation.

Yanagisawa’s development sees him gradually discard his subtlety as his schemes fail, with his obsession driving him to desperate measures. His notable abilities include his genius-level scientific expertise in anti-matter biology, which allowed him to create the tentacle technology at the heart of the conflict. He also utilizes advanced equipment such as a voice modulator and specialized clothing made of anti-sensei fibers to protect himself from his target. In his final confrontation, he mutates his own body into a powerful tentacled monster through self-experimentation, gaining immense physical strength. However, his uncontrollable rage and lack of discipline ultimately prove to be his downfall, as his pride and vengefulness lead him to a defeat that mirrors the destruction he originally caused.