In summary, we presented experimental evidences documenting that UHRF1 downmodulation can sensitize RB cells to HDAC inhibitors by augmenting oxidative stress‐mediated apoptosis via downregulation of GSTA4 and TXN2, along with a newly identified role for UHRF1 in epigenetic repression of photoreceptor genes in RB cells. This evidence concerns the gene HDAC9 and retinoblastoma.