As a result, we found a transcriptional regulatory gene that regulates the stemness of melanoma cells, and revealed that MLLT3 interacted with HMGB1 to inhibit its entry into the nucleus, and MLLT3 interacted with YBX1 to inhibit its reading of m5C of MAGEA1, thereby inhibiting the mRNA stability of MAGEA1, and directly transcribed P53 to inhibit the stemness, proliferation and metastasis of melanoma cells. This evidence concerns the gene HMGB1 and melanoma.