Since the first case detection in Nepal in 1988, the number of cases of Human Immunodeficiency Virus (HIV) are increasing. Limited studies exist concerning the knowledge on HIV among the Nepalese men. This study aimed to examine the social determinants of poor knowledge on HIV among Nepalese men aged 15–49 years based on Nepal Demographic and Health Survey (NDHS), 2011. This study is based on the secondary data of NDHS 2011. HIV knowledge was assessed by using structured qustionnaire. A Chi square test followed by logistic regression was performed to find the association of social determinants with outcome variables. Of the 3,991 participants, 1,217 (30.5 %) had comprehensive knowledge and the majority (69.5 %) had poor knowledge on HIV. More than half (54.6 %) reported that mosquito bite can transmit HIV and 26.5 % reported that sharing food can transmit HIV. Respondents who were uneducated [aOR 10.782; 95 % CI (6.673–17.421)], were manual workers [aOR 1.442; 95 % CI (1.152–1.804)], were poor [aOR 1.847; 95 % CI (1.350–2.570)]; lived in the the Eastern region [aOR 2.203(1.738–2.793)], or in the Mountain [aOR 1.542; 95 % CI (1.132–1.864)]; did not read newspaper/magazine at all [aOR 1.454; 95 % CI (1.142–1.851)] and did not listen to the radio at all [aOR 1.354; 95 % CI (1.046–1.752)] were likely to have poor knowledge of HIV. HIV prevention programs should include men incorporating appropriate educatoinal intervention to increase their knowledge.