This study aimed to investigate the prognostic significance of phosphorylation of TOP1, TOP2A, TOP2B, and C1orf35 in HCC and to characterize their associated molecular features to identify potential diagnostic and therapeutic biomarkers.<h4>Methods</h4>Publicly available HCC phosphoproteomic and proteomic datasets were analyzed to identify significantly upregulated phosphorylation sites of TOP1, TOP2A, TOP2B, and C1orf35. This evidence concerns the gene C1orf35 and hepatocellular carcinoma.