Lung cancer is a major health problem and the leading cause of cancer deaths in the world. The pathogenesis of lung cancer is complex, and is believed to be due to the interaction between environmental and genetic factors. Various evidences show that HPV might be involved in bronchial carcinogenesis. In this study, 141 lung cancer patients and 92 non-cancer control subjects were enrolled to examine whether HPV DNA existed in lung tumor and normal tissues in Mazandaran, north part of Iran by nested PCR. Our data showed that 33 of 129 lung tumors had HPV DNA compared with 8 of 90 non-cancer control subjects (25.6% vs. 9.0%, P=0.002). The infection of HPV had an OR of 3.48 (95% CI 1.522-7.958; P=0.002). Meanwhile infection of high risk HPV types (16 and 18) had a significantly high OR of lung cancer incidence as 8.00 (95% CI 1.425-44.920; P=0.021) compared with 4.423 (95% CI 2.407-8.126; P0.0001) of smoking status. This result suggests that HPV infection is associated with lung cancer development in Mazandaran, Iran.