Myeloid-derived suppressor cells (MDSCs) are thought to play a critical immunosuppressive role in tumorigenesis. In this project, we aimed to investigate subset alteration of MDSCs in gastric cancer (GC), and the effects of epirubicin (EPI) and paclitaxel (TAX) on MDSCs. The frequencies of MDSC subsets in peripheral blood were observed by using flow cytometry after treatment with EPI- or TAX- based chemotherapy in GC patients. After treatment with EPI or TAX in vitro, the subsets, apoptosis, cell cycle, and MAPK and NF-κB protein expressions of mouse bone marrow MDSCs were analyzed. The frequency of MDSCs in the peripheral blood of GC patients was higher than that in healthy controls. Granulocyte-type MDSCs (G-MDSCs) were significantly more than monocyte-type MDSCs (M-MDSCs) in GC patients. The frequencies of MDSC subsets in the peripheral blood decreased after EPI- or TAX-based chemotherapy. High levels of MDSC subsets were correlated with low cancer differentiation degree. High level of M-MDSCs was related to lymph node metastasis, and was negatively correlated with the overall survival of GC patients. After treatment with EPI or TAX, levels of mouse bone marrow MDSC subsets decreased significantly in vitro. Arg-1 secretion and expression of total and phosphorylated MAPK and NF-κB by MDSCs decreased. EPI or TAX decreases the levels of MDSCs, inhibits the proliferation and function of MDSCs in vitro, and induces their apoptosis via the MAPK and NF-κB signaling pathways.