Objective To analyze the influencing factors for post-operative intracranial infection after three-dimensional printing-assisted minimally invasive(3DP-MI) treatment for hypertensive intracerebral hemorrhage (HICH), explore the corresponding preventive measures, so as to provide basis for the formulation of prevention and control measures of post-operative intracranial infection. Methods Clinical data of 324 patients who underwent 3DP-MI treatment in neurosurgery department of a tertiary hospital from October 2015 to December 2018 were retrospectively analyzed, according to whether intracranial infection occurred, patients were divided into infection group and non-infection group, general information and surgical treatment course of two groups of patients were compared. Results Among 324 patients undergoing 3DP-MI treatment, 32 (9.87%) had intracranial infection. 19 strains of pathogens were isolated from specimens of patients with intracranial infection, including 9 strains (47.37%) of Gram-negative bacteria, 8 strains (42.10%) of Gram-positive bacteria, and 2 strains (10.53%) of fungi. Univariate analysis on HICH patients undergoing 3DP-MI treatment showed that differences in smoking history, intracranial hemorrhage volume, time from pre-operative skin preparation to operation, operation location, operation duration, times of post-operative thrombolytic therapy, indwelling time of drainage tube, and prophylactic use of antimicrobial agents were all significantly different (all P < 0.05); multivariate logistic regression analysis showed that prophylactic use of antimicrobial agents was the protective factor for the prevention of intracranial infection, while intracranial hemorrhage volume, time from pre-operative skin preparation to operation, operation duration, indwelling time of drainage tube were independent risk factors for intracranial infection. Conclusion Post-operative intracranial infection in HICH patients undergoing 3DP-MI treatment results from a variety of factors, the key to the prevention of intracranial infection is to take effective prevention and control measures during peri-operative period.