We showed that inhibition of PERK by shRNAs or a small molecular inhibitor enhanced the sensitivity of resistant inactivated PTEN melanoma cells to BRAFi and blocked their growth in vitro and in vivo, suggesting that PERK is a new prognostic marker and therapeutic target for BRAFi-resistant BRAF-mutant melanoma with impaired PTEN. This evidence concerns the gene PTEN and melanoma.