The serine/arginine-rich splicing factors (SRs) belong to the serine arginine-rich protein family, which plays an extremely important role in the splicing process of precursor RNA. The SRs recognize the splicing elements on precursor RNA, then recruit and assemble spliceosome to promote or inhibit the occurrence of splicing events. In tumors, aberrant expression of SRs causes abnormal splicing of RNA, contributing to proliferation, migration and apoptosis resistance of tumor cells. Here, we reviewed the vital role of SRs in various tumors and discussed the promise of analyzing mRNA alternative splicing events in tumor. Further, we highlight the challenges and discussed the perspectives for the identification of new potential targets for cancer therapy via SRs family members.