Objective To assess the influencing factors of pneumothorax incidence after CT-guided percutaneous core needle biopsy. Methods The clinical and imaging data of 597 patients, who underwent CT-guided percutaneous core needle biopsy in Changhai Hospital of Second Military Medical University from Jan. 2013 to Apr. 2015, were retrospectively analyzed. Pearson Chi-square test, continuity-adjusted Chi-square test and Mann-Whitney U test were used to compare the general characteristics, nidus factors and operational factors between the post-operative pneumothorax and non-pneumothorax patients. Parameter estimation and hypothesis test of logistic regression model were used for univariate and multivariate analyses of the above-mentioned parameters. Results The incidence of pneumothorax after CT-guided percutaneous core needle biopsy was 26.97% (161/597). There were significant differences between the post-operative pneumothorax and non-pneumothorax groups in the age, nidus length-diameter, nidus depth, body position, traversing aerated lung, traversing interlobar fissure and traversing subpleural bleb (Z=1.971, Z=3.823, Z=2.169, χ²=29.196, χ²=11.967, χ²=23.353, χ²=29.970; P<0.05, P<0.01). Multivariate analysis showed that the age>68 years old (OR=1.021, 95% CI 1.002-1.040, P=0.032), traversing aerated lung (OR=2.251, 95% CI 1.110-4.566, P=0.025), traversing interlobar fissure (OR=5.092, 95% CI 2.630-9.861, P<0.001) and traversing subpleural bleb (OR=6.313, 95% CI 2.312-17.243, P<0.001) were risk factors of the post-operative pneumothorax, and nidus length-diameter<3.1 cm and supine position were the protecting factors (OR=0.826, 95% CI 0.732-0.933, P=0.002; OR=0.318, 95% CI 0.209-0.483, P<0.001). Conclusion The age, nidus length-diameter, body position (supine), traversing aerated lung, traversing interlobar fissure and traversing subpleural bleb are the influencing factors of pneumothorax incidence after CT-guided percutaneous core needle biopsy.