Hum Paanch is the story of a middle-class white-collar worker, Anand Mathur, who always finds himself in trouble because of his five daughters — Meenakshi, Radhika, Sweety, Kajal, and Chhoti. The three elder daughters are Anand and his first wife's children. The last two are Anand and Bina's daughters. To make matters worse, his first wife is deceased but "haunts" him by speaking to him through her large wall-mounted portrait—usually to nag him or offer sarcastic advice. Living in a chaotic household with his second wife, Bina, Anand tries to maintain order while his daughters hatch various schemes, leading to hilarious misunderstandings and situational comedy.

Rupa Avasthi is the daughter-in-law of a joint family of misfits. She is clumsy and everything she does seems to go wrong somehow.