〔Abstract〕 Objective To investigate the effects of CD98 gene silencing on proliferation, apoptosis and PI3 K/AKT pathway of melanoma B16-F10 cells. Methods shRNA CD98 vector was constructed and transfected into B16-F10 cells. The cells were randomly divided into three groups: Control group, shRNA-NC group and CD98-shRNA3 group for subsequent experiments. Cell proliferation was detected by clone formation assay. Flow cytometry was used to detect apoptosis. Transwell was used to detect cell invasion. Western blot was used to detect the protein expression levels of CD98, Ki67, PCNA, Bax, Bcl-2, Caspase-3, PI3 K, p-PI3 K, AKT, and p-AKT. Results Compared with Control group, group CD98-shRNA3 CD98 protein expression level decreased significantly(P<0.05), clone formation rate decreased significantly(P<0.05), Ki67, PCNA protein expression level decreased significantly(P<0.05), the apoptosis rate increased significantly(P<0.05), Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratio were significantly higher(P<0.05), the number of invasive cells significantly reduced(P<0.05), The ratio of p-PI3 K/PI3 K and p-AKT/AKT significantly reduced(P<0.05). Conclusion CD98 silencing may inhibit the proliferation and invasion of melanoma B16-F10 cells and promote apoptosis by inhibiting the activation of PI3 K/ATK signaling pathway.