In vitro cell experiments mainly explored that (1) IR induced PRMT5 AS by changing the levels of serine/arginine-rich splicing factor 3 (SRSF3) and heterogeneous nuclear ribonucleoprotein H 1 (HNRNPH1); (2) the interaction of SRSF3 and HNRNPH1 involved in the process of PRMT5 splicing; (3) the elevated level of PRMT5-ISO5 sensitized HCC cells to radiation. Here, SRSF3 is linked to hepatocellular carcinoma.