Objective: To establish a difficulty scoring system to predict the difficulty of laparoscopic liver resection (LLR) and to make a preliminary application. Methods: The clinical data of 83 patients undergoing LLR between January 2014 and May 2017 in the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into simple group and difficult group according to the operative time and whether converted to open surgery or not. The factors for surgical difficulty were determined by univariate and multivariate Logistic regression analysis. Then, the scoring system for predicting the surgical difficulty was built based on the coefficient of the regression analysis. The 83 patients were scored and the validity of the scoring system was verified through receiver operating characteristic curve (ROC). Results: The univariate analysis showed that there were significant differences in age, sex, lesion size, lesion traits, distance of the lesion from the inferior vena cava and whether the lesion was located in the left lateral lobe between simple group and difficult group (all P<0.05); multivariate analysis revealed that lesion size (OR=7.034, P=0.043), the distance between the lesion and the inferior vena cava (OR=12.881, P=0.001), and whether the lesion was located in the left lateral lobe (OR=26.774, P=0.001) were independent influential factors for surgical difficulty. The scoring system was established based on the above factors. Efficiency estimation showed that the area under the ROC curve was 0.897 (95% CI=0.826–0.968) with a cut-off value of 4, so the score of a patient equal to or larger than 4 was regarded as surgical difficulty. Conclusion: Surgical difficulty scoring system has certain guiding significance for predicting surgical difficulty in LLR. Surgeons can choose the surgical procedure by referring to the preoperative difficulty score.