Background and Aims Liver function decompensation is the main cause for the increased mortality in patients after liver resection. So, effective preoperative liver function assessment is of great importance. Indocyanine green retention rate at 15 minutes (ICGR₁₅) is a simple and accurate test to evaluate preoperative liver function and is widely used in clinical practice. ICGR₁₅ <20% is essential to major hepatectomy (≥3 segments). Patients with ICGR₁₅ value ranging from 20% to 30% are frequently encountered in clinical practice, and their ICGR₁₅ can be improved after symptomatic management such as hepatoprotective treatment. Whether the major hepatectomy can be safely performed in these patients remains controversial. Therefore, this study was to evaluate the effectiveness of preoperative ICGR₁₅ improvement on complications and liver function in patients after hepatectomy for liver cancer.Methods Form May 2015 to October 2017, 32 liver cancer patients whose ICGR₁₅ values were between 20% and 30% on admission and were improved to less than 20% after symptomatic treatment before operation (observation group), and the other 45 liver cancer patients with the ICGR₁₅<20% on admission (control group) were selected. All patients underwent open liver cancer resection (≥3 segments). The intra- and postoperative variables, and the total bilirubin (TBIL), aspartate aminotransferase (AST), albumin (Alb), and prothrombin time (PT) as well as the ECOG physical status scores were compared between the two groups of patients.Results Between the two groups of patients, except the ICGR₁₅ values on admission that were significantly different (P<0.05), all other preoperative general data and biochemical indexes showed no statistical difference (all P>0.05). There were no statistical differences in liver resection scopes and other intraoperative variables between the two groups of patients (all P>0.05). No perioperative death occurred in both groups, and the incidence rates of postoperative complications were 37.5% (12/32) in observation group and 31.1% (14/45) in control group, which had no statistical difference (P>0.05). The length of hospital stay and time to drainage tube removal were prolonged in observation group compared with control group (both P<0.05). The levels of TBIL at hospital discharge or 1 month, and 3 and 6 months after operation were all significantly higher in observation group than those in control group (all P<0.05). The levels of ALB and ECOG scores at hospital discharge or 1 month after operation were all significantly lower in observation group than those in control group (all P<0.05), but both variables showed no significant differences between the two groups later (all P>0.05). There were no significant differences in the remaining biochemical indexes between the two groups at each time point from the time of hospital discharge to 6 months after operation (all P>0.05).Conclusions Patients with the preoperative ICGR₁₅ between 20% to 30% can tolerate major hepatectomy safely after improvement of ICGR₁₅ to less than 20% by hepatoprotective treatment, without increase of postoperative complications. Although the TBIL level is relatively high during a short period after operation, it does not exert harmful effect on patients' quality of life. However, the long-term results of the patients still need further observations.