Objective To explore risk factors and treatment strategies of liver resection surface infection following laparoscopic hepatolithiectomy for patient with complicated intrahepatic bile duct stones. Methods The clinical data of 45 patients with complicated intrahepatic bile duct stone underwent laparoscopic hepatectomy from January 2014 to April 2017 in this hospital were analyzed. The liver resection surface infection rate, pathogenic bacteria distribution, factors of operation, antibiotic use time, volume of drainage, and drainage tube placement time were analyzed. Results A total of 13 cases of liver resection surface infection occurred following the laparoscopic hepatolithiectomy in the 45 cases, the infection rate was 28.89%. Totally 24 strains of pathogens were isolated from the infected patients, including 9 strains of gram-positive bacteria and 15 strains of gram-negative bacteria. The mainly postoperative complications included 16 cases of the biliary leakage, 5 cases of the effusion and empyema, the average drainage volume was about 200 mL after the surgery. The double pipes were placed in the 10 patients in the operation. The drainage tubes were placed in the 23 patients under the ultrasound or CT intervention after the surgery, the average time of drainage tube placement was 8 d. The results of univariate analysis showed that the past biliary surgery history, combined with liver cirrhosis, double pipe drainage, operation time, and postoperative biliary leakage were associated with the liver section surface infection following the laparoscopic hepatolithiectomy (P<0.050). The results of multivariate analysis identified that the past biliary surgery history and postoperative biliary leakage were the risk factors (P<0.050), while the double pipe drainage was the protective factor (P<0.050) for liver resection surface infection following the laparoscopic hepatolithiectomy. Conclusions Prophylactic treatment such as perfect preoperative management and careful intraoperation should be taken for risk factors of liver section surface infection following laparoscopic hepatolithiectomy. Actively effective treatment strategies should be given if postoperative liver section surface infection existence.