Hepatocellular carcinoma (HCC) is one of themost lethal and malignant types of cancer that affects globalhuman health. The present study aimed to investigate theeffect of pyruvate kinase muscle isozyme M2 (PKM2)expression on the clinical features and prognosis of HCC.The present study employed univariate logistic regression toinvestigate the correlation between PKM2 expression andclinical features. Univariate and multivariate Cox regressionanalyses were performed to estimate the independent effect ofPKM2 expression on survival status. The results revealed thatpatients in the high PKM2 group (≥11.25) exhibited signifi-cantly lower creatinine levels (P=0.043), higher fetoproteinlevels (P<0.001), advanced stage (P<0.001) and higher grade(P=0.004) compared with patients with low PKM2 expres-sion levels (<11.25). In addition, patients with high PKM2expression exhibited poor prognosis compared with patientswith low PKM2 expression. After correcting the covariates,PKM2 expression remains significantly associated withreduced overall survival (P<0.05). These findings suggestedthat PKM2 is an independent risk factor for HCC and providesvaluable information for future studies on the pathogenesis ofHCC and drug discovery.