Protein arginine methyltransferase 5 (PRMT5) is an epigenetic regulator, and we found that SRSF3 and HNRNPH1 competitively bind to PRMT5 pre-mRNAs located in the region around the 3′- splice site on intron 2 and selective 3′- splice site on exon 4, generating the long isoform of PRMT5L to promote hepatocellular carcinoma progression. The gene discussed is SRSF3; the disease is hepatocellular carcinoma.