The story centers on the relationship between a male otaku named Tibet and his yaoi-obsessed fujyoshi girlfriend Yaoi whose obsession manifests itself as a small, green furry monster.
Tonari no 801-chan is narrated by Tibet (チベット, Chibetto?), otherwise known as Tibe-kun (チベ君, Chibe-kun?), a twenty-eight-year-old company employee and boyfriend to Yaoi, otherwise known as Yaoi-chan (801ちゃん, Yaoi-chan?). Yaoi, who also works in a company, is a twenty-two-year-old fujyoshi, a female otaku who is a fan of anime and manga series featuring yaoi, or romantic relationships between men. Tibet, who is an otaku himself, initially met Yaoi over the Internet. When she obsesses over yaoi, a small green furry monster comes out of a zipper from her back as the manifestation of her obsession.