Significant portal hypertension (SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma (HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH.HCC patients with cirrhosis who underwent laparoscopic liver resection (LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching (PSM) analysis was performed to minimize bias.A total of 165 patients were divided into two groups based on the presence (SPH, n = 76) or absence (non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group (P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate (n = 0), overall postoperative complications (47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification (P = 0.347), conversion to open surgery (9.2% vs. 6.7%, P = 0.557), or length of hospitalization (16 vs. 15 days, P = 0.203) between SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM (log-rank P > 0.05).After PSM, alpha-fetoprotein (AFP) ≥ 400 μg/L [hazard ratio (HR) = 4.71, 95% confidence interval (CI): 2.69-8.25], ascites (HR = 2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists (ASA) classification (III vs. II) (HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm (HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS.LLR for patients with HCC complicated with SPH appears feasible at the price of increasing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.Copyright © 2022. Published by Elsevier B.V.