Human immunodeficiency virus (HIV) has been widely prevalent among older men (aged ≥50 years old) in Sichuan Province. The study aimed to discover associated factors with the new HIV infection in older men, and provide a scientific basis for the prevention and control of acquired immunodeficiency syndrome (AIDS) in this group. A cross-sectional survey study of newly reported HIV/AIDS and general male residents aged 50 years and older was conducted between April and June 2019, with a resample of respondents to identify cases and controls, followed by a case-control study. Logistic regression was applied to analyse the association between the selected factors and new HIV infection among older men. At last, 242 cases and 968 controls were included. The results of multiple logistic regression suggested that many factors including living alone/concentrated (OR 1.56, 95% CI 1.20-2.04, P = 0.001), have a history of migrant worker (OR 2.10, 95% CI 1.61-2.73, P < 0.001), have commercial sexual behaviour (OR 1.71, 95% CI 1.32-2.22, P < 0.001), married (OR 0.48, 95% CI 0.37-0.64, P < 0.001), have a history of HIV antibody testing (OR 0.73, 95% CI 0.56-0.96, P = 0.026), HIV-related knowledge (OR 0.55, 95% CI 0.42-0.72, P < 0.001) were associated with new HIV infection among older men. The present study revealed some potential risky/protective factors altogether. The results highlighted the direction of HIV/AIDS prevention and control among older men, and it is a social issue that requires the joint participation of the whole society.