Melanoma is an aggressive cutaneous malignancy. In this study, we demonstrated that the levels of the programmed cell death 4 (PDCD4) protein and mRNA were lower in tumor tissues compared with normal tissues. In order to further investigate the effects of PDCD4 and its fragments in B16 melanoma cells, we established B16 clones with expression of different PDCD4 fragments. Intact PDCD4, PDCD4∆164‑469 and PDCD4∆327-440 expression, respectively, decreased proliferation and migration and increased apoptosis in B16 cells in vitro. We found that intact PDCD4, PDCD4∆164-469 or PDCD4∆327-440 can inhibit the activity of MMP-2 and the expression of CXCR4. However, PDCD4∆164-275 showed no effects on B16 cells. These results may prove helpful for the development of novel therapies for melanoma treatment.