High G6PD expression levels were detected in CK19-positive lesions and early preneoplastic foci, but not in CK-19-negative lesions, and, in line, increased G6PD mRNA levels were observed in two HCC patient cohorts where it positively correlated with CK19 expression, higher tumor grade, and increased metastasis formation. Here, G6PD is linked to hepatocellular carcinoma.