Nucleotide synthesis inhibitors have already been available as antineoplastic agents for cancer therapy and several enzymes relevant to pyrimidine metabolism are clinically approved as treatment options.[8] Here, we found that TRIM65 could up‐regulate numerous metabolites in the uracil pathway, which served as nucleotides and as an energy source for cellular metabolism, promoting the rapid proliferation of HCC cells. This evidence concerns the gene TRIM65 and cancer.