Myeloid-derived suppressor cells (MDSCs) are known to accumulate during chronic viral infection, including human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) infection, and play a critical role in suppressing immune responses. However, the role of MDSCs in HIV/HCV coinfection is unclear. Here, we observed a dramatic increase in monocytic MDSCs (M-MDSCs) level in the peripheral blood of HIV/HCV-coinfected patients compared to that of healthy controls; the level of M-MDSCs proportion in coinfection was not higher than that in HIV or HCV monoinfection. Interestingly, we found the M-MDSCs level in coinfected patients correlated well with CD4+ T cell loss (r = −0.5680; P = 0.0058), HIV-1 load (r = 0.6011; P = 0.0031), HCV load (r = 0.6288; P = 0.0017) and activated CD38+ T cells (r = 0.5139; P = 0.0144). Initiation of highly active antiretroviral therapy considerably reduced both M-MDSCs and CD8+CD38+-activated T cell proportion in coinfected patients, and they showed a parallel course of decline. Thus, our results suggest that HIV-1 infection and high chronic immune activation may contribute to the expansion of M-MDSCs and accelerate the disease progression in HIV/HCV-coinfected patients.