Collectively, our findings found that TRPV4 is functionally overexpressed in melanoma and established the principle of targeting TRPV4 to inhibit metastasis, as well as revealed that Baicalin might serve as a natural small molecule inhibitor of TRPV4 that may be further optimized to be a therapeutic agent to attenuate metastasis of melanoma. This evidence concerns the gene TRPV4 and melanoma.