Background: To investigate the feasibility of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC), we compared the outcome between LLR and conventional open liver resection (OLR) in patient groups with different IWATE criteria difficulty scores (DS). Methods: We retrospectively reviewed 607 primary HCC patients (LLR: 81, OLR: 526) who underwent liver resection in Linkou Chang Gung Memorial hospital from 2012 to 2019. By using 1:1 propensity score-matched (PSM) analysis, their baseline characteristics and the DS stratified by the IWATE criteria were matched between the LLR and OLR. Their perioperative and oncologic outcomes were compared. Results: After 1:1 PSM, 146 patients (73 in LLR, 73 in OLR) were analyzed. Among them, 13, 41, 13 and 6 patients were classified as low, intermediate, advanced and expert DS group, respectively. Compared to OLR, the LLR had shorter hospital stay (9.4 vs. 11.5 days, p = 0.071), less occurrence of surgical complications (16.4% vs. 30.1%, p = 0.049), lower rate of hepatic inflow control (42.5% vs. 65.8%, p = 0.005), and longer time of inflow control (70 vs. 51 min, p = 0.022). The disease-free survival (DFS) and overall survivals were comparable between the two groups. While stratified by the DS groups, the LLR tended to have lower complication rate and shorter hospital stay than OLR. The DFS of LLR in the intermediate DS group was superior to that of the OLR (p = 0.020). In the advanced and expert DS groups, there were no significant differences regarding outcomes between the two groups. Conclusion: We have demonstrated that with sufficient experience and technique, LLR for HCC is feasible and the perioperative outcome is favorable. Based on the current study, we suggest LLR should be a standard procedure for HCC with low or intermediate difficulty. It can provide satisfactory postoperative recovery and comparable oncological outcomes. Further larger scale prospective studies are warranted to validate our findings.