Here, we noted that knockdown and knockout of HO-1 in melanoma cells significantly downregulated both CDK2 and cyclin E protein levels, whereas HO-1 overexpression could reverse these effects on CDK2 and cyclin E. Finally, via rescue methods in HO-1−/− cells, this study provided proof that the HO-1- cells induced changes in the cell cycle through the cyclin E and CDK2 regulatory proteins were associated with B-Raf expression. Here, CCNE1 is linked to melanoma.