Objective To identify the risk factors of corneal endothelial cell injury caused by phacoemulsification, so as to provide the evidence for formulating interventions for prevention of corneal endothelial cell injury among cataract patients. Methods A total 248 eyes from 212 cataract patients that underwent phacoemulsification were selected as study subjects. The associations of subjects’ age, gender, left/right eye, pupillary diameter, grades of lens nucleus hardness, duration of phacoemulsification, total ultrasound energy, total infusion fluid amount with endothelial cell loss were evaluated using univariate analysis, and the independent risk factors for corneal endothelial cell injury caused by phacoemulsification were identified using multiple linear regression analysis. Results The density of endothelial cells was (2282.4 ± 412.16) cells/mm² prior to phacoemulsification and (1921.77 ± 125.46) cells/mm² months after phacoemulsification in 239 affected eyes, and the proportion of endothelial hexagonal cells was (54.41 ± 7.22)% prior to phacoemulsification and (45.62 ± 3.58)% months after phacoemulsification (χ² = 5.43, P < 0.05). The incidence of corneal endothelial cell injury was 15.5% in 239 affected eyes. Univariate analysis showed that advanced age, small pupillary diameter, long duration of phacoemulsification, high grades of lens nucleus hardness and high total ultrasound energy were associated with endothelial cell loss, while gender and surgical eyes (left or right eye) were not associated with endothelial cell loss. Multiple linear regression analysis revealed that high grades of lens nucleus hardness, high total infusion fluid amount, long duration of phacoemulsification and high total ultrasound energy were independent risk factors for endothelial cell loss. Conclusions Lens nucleus hardness, high totalinfusion fluid amount, long duration of phacoemulsification and high total ultrasound energy are independent risk factors for endothelial cell loss caused by phacoemulsification.