Puliyoor is small village ridden by forest and people lives on the verge of attacks from man-eating tigers which is called by the name Varayan Puli. Murugan, a lorry driver who hunt and kills such rogue tigers, lives in this village with his wife Myna and daughter Chakki. His father was killed by a tiger and the young Murugan took his vengeance by killing the tiger with the help of his uncle Balaraman and earns the name Pulimurugan amongst villagers. One day, a hooded stranger drops in the village looking for Pulimurugan to rope in him for a hunting assignment. Village chief tells him about Murugan.
Once Murugan has been away from Puliyoor and many people have been killed in the attack of tigers. Murugan's younger brother Manikuttan who studies MBA in Banglore sends his two friends, Shiva and Benny, to the village. Shiva's father Daddy Girija owns a pharmaceutical company which is developing a drug for cancer using marijuana. Hearing that Manikuttan will be offered a job in the company, Balaraman help them to sign a contract with a Ramaiya, an illegal ganja dealer in the forest. On their way back, Shiva and Benny come to face to face with a tiger and are saved by Pulimurugan who kills the tiger.
The police find the carcass of the tiger and they register a case. The investigation is handed over to forest ranger RK who has a grudge against Murugan. And Murugan is forced to hide. Meanwhile, Ramaya gets arrested and fearing that the information is leaked, Pulimurugan with his family is made to escape to Mangalore where he earns the trust of Daddy Girija. Meanwhile, Manikuttan gets the job he was offered.
Later Murugan finds out that Daddy Girija is running a hash oil business under the cover of pharmaceuticals. Manikuttan co-operates with police to catch Daddy Girija but Shiva who learns about it tortures him. Murugan while saving Manikuttan accidentally kills Shiva. Daddy Girija makes an escape from police.
It turns out that the stranger in the hood was actually Daddy Girija who has arrived with a pack of henchmen to take his revenge on Murugan. What follows is a thrilling action.
Pulimurugan which opened to fantastic run at the box office went on to become the highest ever grossing Malayalam film. It was later dubbed into Tamil in the same title and Telugu in the title Manyam Puli. Sher Ka Shikaar, a Hindi dubbed version, was released on television. Pulimurugan fetched many accolades including Special Jury mention for Mohanlal and Best Stunt Choreographer for Peter Hein at the National Awards.