This study was to evaluate the cellular inhibition effects induced by anti-AGR2 monoclonal antibody 18A4 in two AGR2-negative melanoma cells, A375 and B16-F10, treated with external oncoprotein AGR2. MTT assay and colony formation assay were performed to detect the cell proliferation rate. Flow cytometry analysis was performed to evaluate cell cycle transition. Cell migration rate was analyzed by wound healing assay. Cell morphological changes were detected by phalloidin staining. The expression of p53 was detected by Western blotting and immunofluorescence. Results showed that 18A4 inhibited the AGR2-dependent tumor properties including enhanced proliferation, accelerated cell cycle, increased cell migration and morphological changes of cells. In addition, by Western blot analysis and immunofluorescence, AGR2 blocking antibody 18A4 also restored p53 expression that was repressed by external AGR2 treated by chemotherapeutic drug doxorubicin. These findings suggest that 18A4 is able to inhibit the cellular tumorigenic properties induced by external AGR2 and is a potential drug against fumor.