ABSTRACTWe evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist‐prothrombin (PIVKA‐π), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA‐π and pathological features of HCC. Plasma levels of PIVKA‐π and α‐fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA‐π was detected (≥ 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA‐π produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (<100 ng/mL) levels were positive for PIVKA‐π. No apparent relationship, however, could be found between the levels of PIVKA‐π and the aetiology or pathological findings of HCC. These results suggest that PIVKA‐π can be a reliable marker for detecting HCC in