In this study, the findings revealed that LHFPL3-AS1-long, one of two LHFPL3-AS1 isoforms, was required for maintaining the stemness of melanoma stem cells via directly interacting with miR-181 to inhibit the mRNA degradation of its target gene Bcl-2 and apoptosis of melanoma stem cells. This evidence concerns the gene LHFPL3 and melanoma.