Our aims were to compare the therapeutic efficacy of surgical resection of caudate lobe hepatocellular carcinoma and noncaudal lobe hepatocellular carcinoma in the Chinese population. The study group consisted of 220 patients undergoing caudate lobe hepatectomy during the period spanning from January 2003 to November 2017, and 220 patients with caudate lobe hepatectomy were selected as the control group. There were 142 cases (64.5%) of surgical margin of R0 in patients with caudate lobe liver cancer, and 178 cases (80.9%) of surgical margins in patients with noncaudal lobe liver cancer, and the difference was statistically significant (P<0.01) between the 2 groups. Compared with noncaudal lobe liver cancer patients, caudate lobe liver cancer patients had significantly longer operation time (186.65±81.36 vs. 118.85±69.23, P<0.01), longer vessel block time (29.93±11.96 vs. 22.76±10.74, P<0.01), more intraoperative blood loss (709.73±108.39 vs. 329.74±85.76, P<0.01), and there was no significant difference in the incidence of complications (53.4% vs. 46.6%, P>0.05). Significantly different therapeutic efficacy was found between the caudate lobe hepatocellular carcinoma group and the noncaudal lobe hepatocellular carcinoma group, which may be due to the lack of resection margin of caudate-leaf liver cancer surgery and more intraoperative bleeding.