Highway Killers tells the story of two friends who rent a car and start killing people who cross their path. The two men, who set out on the road after renting a car, begin robbing shops and gas stations along the highway under the influence of heavy drugs. Meanwhile, the pair, who start killing people who cross their path with a pump-action shotgun, make plans to flee the country via the southern border.

Beren is a young girl preparing for her university entrance exams. After returning from a camp she attended, Beren suddenly falls ill. At this time, her father Salih is abroad for work, and her stepmother Nurdan, who loves her like her own daughter, calls her brother Doğu to stay with them, thinking it will be good for her. However, shortly after Doğu and his wife Nergis arrive, events unfold that will deeply affect everyone's lives. Because Beren has become physically and psychologically ill due to a spell cast on her.