SPC25 is significantly upregulated in HCC (p < 0.001) with high diagnostic value (AUCs of 0.969 and 0.945). High SPC25 expression correlates with poor prognosis (p < 0.001) and independently predicts OS, with a nomogram consistency index higher than the AJCC staging system. The gene discussed is SPC25; the disease is hepatocellular carcinoma.