Background: Studies have shown that hepatitis C virus (HCV) infection increased during the past decades in China. However, little evidence is available on when, where, and who were infected with HCV. There are gaps in knowledge on the epidemiological burden and evolution of the HCV epidemic in China. Methods: Data on HCV cases were collected by the disease surveillance system from 2005 to 2012 to explore the epidemic in Henan province. Spatiotemporal scan statistics and age-period-cohort (APC) model were used to examine the effects of age, period, birth cohort, and spatiotemporal clustering. Results: 177,171 HCV cases were reported in Henan province between 2005 and 2012. APC modelling showed that the HCV reported rates significantly increased in people aged > 50 years. A moderate increase in HCV reported rates was observed for females aged about 25 years. HCV reported rates increased over the study period. Infection rates were greatest among people born between 1960 and 1980. People born around 1970 had the highest relative risk of HCV infection. Women born between 1960 and 1980 had a five-fold increase in HCV infection rates compared to men, for the same birth cohort. Spatiotemporal mapping showed major clustering of cases in northern Henan, which probably evolved much earlier than other areas in the province. Conclusions: Spatiotemporal mapping and APC methods are useful to help delineate the evolution of the HCV epidemic. Birth cohort should be part of the criteria screening programmes for HCV in order to identify those at highest risk of infection and unaware of their status. As Henan is unique in the transmission route for HCV, these methods should be used in other high burden provinces to help identify subpopulations at risk.