Hepatitis C virus (HCV) infection is a public health issue worldwide. Injecting drug use remains the major mode of transmission in developed countries. Monitoring the HCV transmission dynamic over time is crucial, especially to assess the effect of harm reduction measures in drug users (DU). Our objective was to estimate the prevalence and incidence of HCV infection in DU in France using data from a repeated cross-sectional survey conducted in 2004 and 2011. Age- and time-dependent HCV prevalence was estimated through logistic regression models adjusted for HIV serostatus or injecting practices. HCV incidence was estimated from a mathematical model linking prevalence and incidence. HCV prevalence decreased from 58·2% [95% confidence interval (CI) 49·7–66·8] in 2004 to 43·2% (95% CI 38·8–47·7) in 2011. HCV incidence decreased from 7·9/100 person-years (95% CI 6·4–9·4) in 2004 to 4·4/100 person-years (95% CI 3·3–5·9) in 2011. HCV prevalence and incidence were significantly associated with age, calendar time, HIV serostatus and injecting practices. In 2011, the highest estimated incidence was in active injecting DU (11·2/100 person-years). Given the forthcoming objective of generalizing access to new direct antiviral agents for HCV infection, our results contribute to decision-making and policy development regarding treatment scale-up and disease prevention in the DU population.