Melanoma is a malignant tumor produced by highly aggressive and metastatic melanocytes. NRAS mutation is a relatively common mutation in melanoma cells. Mitogen-activated protein kinase (MAPK) signaling pathway and the PI3K/Akt pathway in melanoma cells are relatively common signaling pathways. In this study, we investigated the effect of inhibition of Axl expression on the targeted inhibition of the PI3K/Akt pathway in NRAS-mutant melanoma cells. In this study, immunohistochemistry and western blot methods were used to detect the expression of Axl and Akt proteins in melanoma cells. Axl inhibitor was added, and it detected the inhibitory efficiency of Akt inhibitor in melanoma cells. Finally, a melanoma mouse model was established, and it detected the proliferation and apoptosis of mouse tumor cells induced by Axl inhibitor and Akt inhibitor. The results showed that Axl and Akt were highly expressed in NRAS-mutant melanoma cells, and stimulation of Axl expression could reduce the inhibitory effect of Akt inhibitor on melanoma cells. The addition of Axl inhibitor can synergistically promote the effect of Akt inhibitor, slow down the proliferation of tumor cells, and induce cell apoptosis. According to the experiment in this study, Axl inhibitor combined with Akt inhibitor has a stronger therapeutic effect on melanoma than Akt inhibitor alone.