We demonstrate the physiological, functional and clinical relevance of the spliced 3′ UTR of the key oncogene CTNNB1. We show that CTNNB1 is over-spliced in ~40% of tumour samples in ten cancer types, and its spliced 3′ UTR (1) is a more robust prognostic indicator compared with its transcript expression and somatic mutational status in HCC; (2) is not an NMD target; (3) promotes cell proliferation and migration; and (4) enhances protein expression potentially through its cytoplasmic localization (Fig. 8e). Here, CTNNB1 is linked to cancer.