Melanoma is a malignant tumor with high degree of malignancy, metastasis and high mortality. the proliferation and metastasis of A375 and A875 cells in a concentration-dependent manner. Fangchinoline inhibited the proliferation of A375 and A875 cell Vegfa activity with IC50 values of 12.41 and 16.20 M. We also found that fangchinoline could significantly reduce the phosphorylation of Focal adhesion kinase (FAK). In summary, we demonstrated that fangchinoline inhibits the proliferation and metastasis of melanoma cells by suppressing FAK and its downstream signaling pathway. More importantly, we provide a novel mechanism that fangchinoline could be an effective candidate for the treatment of melanoma. S. Previous reports showed that, fangchinoline could induce cell cycle arrest, apoptosis Arry-380 and metastasis in cultured cancer cells. Fangchinoline may be a potential drug candidate for the prevention of lung cancer by the downregulation of cellular CDK4, CDK6 and cyclin D1 levels then blocking cell cycle progression (6). Fangchinoline could target PI3K in tumor cells Arry-380 that express PI3K abundantly and inhibit the growth and metastasis ability of SGC7901 cells (23). Studies showed that fangchinoline induced G1/S arrest by modulating expression of p27, PCNA and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenografts (7,9). Fangchinoline also induced autophagic cell death via p53/sestrin2/AMPK signaling in human hepatocellular carcinoma cells (24). Reports also indicated that fangchinoline inhibited cell proliferation via Akt/GSK-3/cyclin D1 signaling and induce apoptosis in MDA-MB-231 breast cancer cells (10,11,25). Researchers pointed out that fangchinoline could achieve the inhibition of lung cancer and glioma Arry-380 role by regulating multiple signaling pathways (26,27). Many reports pointed out that fangchinoline could inhibit cell proliferation, promote cell apoptosis, inhibit cell metastasis and inhibit tumor angiogenesis to achieve the purpose of inhibiting the occurrence and development of tumors. However, there was no report on whether fangchinoline could play the same role in melanoma cells as in other cancer cells. In the present study, we observed the effect of fangchinoline on Arry-380 different cell line proliferation through the MTT assay. The results showed that fangchinoline inhibited melanoma cell proliferation dose-dependently. The flow cytometry experiment pointed out that fangchinoline could repress the cell cycle from G1 to S phase transformation. The effect of this was through the inhibition of cyclin D1. At the same time we found that apoptosis of fangchinoline could promote the apoptosis of melanoma. In addition, through Transwell experiments we found that fangchinoline regulated the proliferation of melanoma cells, and it could inhibit melanoma cell metastasis through inhibiting paxillin. By detecting the protein level and mRNA level of FAK and FAKp-Tyr397 we found that these functions weere likely to be due to the inhibition of fangchinoline by phosphorylation of FAK. We found that when FAK inhibitor was added the inhibition of fangchinoline to melanoma cell growth and metastasis almost disappeared, which confirmed that the inhibitory effect of fangchinoline on growth and metastasis of melanoma cells may be achieved by inhibiting the phosphorylation of FAK in the opposite direction. In summary, our data clarified that fangchinoline could inhibit the growth and metastasis of melanoma cells by inhibiting FAKp-Tyr397 Arry-380 and suppressing the FAK pathway. Although further tests are needed to confirm our results, our data can still provide a certain experimental basis for the treatment of melanoma..