Background: Researches comparing laparoscopic liver resection (LLR) with microwave ablation (MWA) for 3-5 cm multifocal hepatocellular carcinoma (MFHCC) are rare. Materials and methods: From 2008 to 2019, 666 intrahepatic tumours in 289 patients from 12 tertiary medical centres in China were included in this retrospective study. Propensity score matching (PSM) was performed to balance variables between the two treatment groups over time frames 2008-2019 and 2013-2019 to observe the potential impact of advancements in intervention techniques on overall survival (OS), disease-free progression (DFS) of patients. complications, hospitalization, and cost were compared. Results: Among 289 patients, the median age was 59 years [interquartile range (IQR) 52-66]. 2008-2019, after PSM, the median OS was 97.4 months in the LLR group and 75.2 months (95% CI 47.8-102.6) in the MWA group during a follow-up period of 39.0 months. The 1-year, 3-year and 5-year OS rates in the two groups were 91.8%, 72.6%, 60.7% and 96.5%, 72.8%, 62.5% [hazard ratio (HR) 1.03, 95% CI 0.62-1.69, P =0.920]; The corresponding DFS rates were 75.9%, 57.2%, 46.9%, and 53.1%, 17.5%, 6.2% (HR 0.35, 95% CI 0.23-0.54, P <0.001). 2013-2019, the median OS time was not reached in either group during the 34.0 months of follow-up, the 1-year, 3-year and 5-year OS rates in the two groups were 90.2%, 67.6%, 56.7% and 96.5%, 76.7%, 69.7% (HR 1.54, 95% CI 0.79-3.01, P =0.210); The corresponding DFS rates were 69.6%, 53.9%, 43.3%, and 70.4%, 32.1%, 16.5% (HR 0.68, 95% CI 0.41-1.11, P =0.120). The incidence of major complications was similar in both groups (all P> 0.05). MWA had shorter intervention times, hospitalization, and lower costs. Conclusions: For resectable MFHCC patients, LLR is preferable due to its lower recurrence rate. For patients who do not qualify for LLR, advances in ablation technology have promoted MWA as a promising alternative.