Protein arginine methyltransferase 7 (PRMT7) regulates various cellular responses, including gene expression, cell migration, stress responses, and stemness. In this study, we investigated the biological role of PRMT7 on cell cycle progression and DNA damage response (DDR) by inhibiting PRMT7 activity with either SGC8158 treatment or its specific siRNA transfection. Suppression of PRMT7 caused cell cycle arrest at G₁ phase, resulting from a stabilization and subsequent accumulation of p21 protein. In addition, PRMT7 activity is closely associated with DNA repair pathways, both homologous recombination and non-homologous end-joining. More interestingly, SGC8158, in combination with doxorubicin, led to a synergistic increase in both DNA damage and cytotoxic effects of doxorubicin. Altogether, our data demonstrate that PRMT7 is critical modulator for cell growth and DDR, indicating a promising target for cancer treatment.