PurposeTo determine the predictive value of portal hypertension (PH) for the development of post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). Patients and methodsThis study enrolled a total of 659 patients with HCC that received hepatectomy as a first-line therapy. PH was classified as grade 0, 1, and 2 according to whether the indirect criteria for PH were met: 1) patients had obvious varicose veins and 2) splenomegaly was present and platelet count < 100 x 10(9)/L. The effects of each variable on the occurrence of PHLF were assessed using univariate and multivariate analyses. ResultsPH grade 2 (odds ratio [OR] = 2.222, p = 0.011), higher age (OR = 1.031, p = 0.003), hepatitis C infection (OR = 3.711, p = 0.012), open surgery (OR = 2.336, p < 0.001), portal flow blockage (OR = 1.626, p = 0.023), major hepatectomy (OR = 2.919, p = 0.001), hyperbilirubinemia (>= 17.2 mu mol/L, OR = 2.113, p = 0.002), and high levels of alpha-fetoprotein (> 400n g/ml, OR = 1.799, p = 0.008) were significantly associated with PHLF occurrence. We performed a subgroup analysis of liver resection and found that the extent of liver resection and PH grade were good at distinguishing patients at high risk for PHLF, and we developed an easy-to-view roadmap. ConclusionPH is significantly related to the occurrence of PHLF in patients who underwent hepatectomy. Noninvasively assessing PH grade can predict PHLF risk.