Here, we report that depletion of PHF19L causes upregulation of CDKN1A/p21 and downregulation of several genes essential for the control of cell cycle, such as CCNA2, CCNB2, CDK4, E2F1, and AATF. Consistent with changes in gene expression, we observed strong decreases in cell growth and proliferation after PHF19L depletion in both prostate cancer cell lines. This evidence concerns the gene E2F1 and prostate cancer.