Our findings revealed that the hnRNP A2B1-mediated splicing triggered the upregulation of TPPP3, DOCK2, and EIF3H, and the downregulation of RNF128, DAPK1, and SYT7 in melanoma stem cells, leading to the suppression of apoptosis of cancer stem cells. Here, HNRNPA2B1 is linked to melanoma.