The HIV/AIDS epidemic caused by commercial blood donation in rural Henan Province of China in the early- to mid-1990s is the largest known cohort in the world related to blood donation but is not fully described. The objectives of this study were to describe the epidemic, epidemiology, and social epidemiology of commercial blood donation and HIV/AIDS. Both qualitative and quantitative mixed methods were used. A village was randomly selected from the 38 key HIV/AIDS pandemic villages in Henan Province. "Demographic Data Form" was applied to collect demographic information of each resident. Focus groups were held for the managers, some residents, members of "HIV/AIDS Work-Team" (organized by the Henan Provincial Government) in the village. Every village physician, people living with HIV/AIDS (PLWHA), school header, and other stakeholders were interviewed individually. The social epidemiology of HIV/AIDS was analyzed under three perspectives of the framework: individual, social, and structural perspectives. In this village, there were 2335 residents, 484 (20.3%) were former donors, 107 (4.6%) were PLWHA, and 96.3% of PLWHA were infected through commercial blood donation. Individually, low education and plasma donation were the risky factors of HIV/AIDS infection. Socially, the epidemic was geography-, kinship-, and conformity-related. Structurally, the related macrostructure factor was policy endorsement of national blood products. The microstructure factors were poverty and value belief on male child in passing down generations. It is concluded that commercial blood donation and HIV/AIDS epidemic in the village are symbiotically related. The epidemic is temporary and socially determined.