The present study provides original and compelling data demonstrating that a high proportion of spliceosomal elements is altered in HCC in comparison with NTAT, including key spliceosome components and splicing factors, such as EIF4A3, ESRP2, SRPK1 and RBM3, which were consistently validated in seven additional in silico cohorts (at mRNA or protein levels). Here, RBM3 is linked to hepatocellular carcinoma.