One Friday Night is a suspense-thriller that revolves around the life of a wealthy childless couple named Ram Varma (Milind Soman) and Dr. Lata Varma (Raveena Tandon). Ram is a businessman who is in a covert relationship with Nirosha Patel (Vidhi Chitalia), a girl half his age. On a stormy rainy night, Ram and Nirosha secretly meet at the former's villa where the latter reveals that she is pregnant with his child. Things take a dramatic twist when a life-changing accident leaves Ram critically injured at the villa which prompts Nirosha to immediately call for medical help. With all helplines down and no option available, Nirosha contacts Lata for medical help and reveals the truth about herself and Ram. What follows next is a string of surprises and a complete rollercoaster ride.