Objective: To analyze the association between preoperative high-density lipoprotein cholesterol (HDL-C) and acute kidney injury (AKI) in patients after cardiac surgery with cardiopulmonary bypass (CPB). Methods: We conducted a retrospective analysis of clinical data from adult patients who underwent cardiac surgery with CPB. The patients were divided into low HDL-C level group (<1.04 mmol·L-1) and normal HDL-C level group (≥ 1.04 mmol·L-1) according to the preoperative blood lipid level. The clinical data and the incidence of postoperative AKI within 7 days after surgery were compared between the two groups. Univariate analysis and binary Logistic regression analysis were used to evaluate the effect of preoperative HDL-C concentration on postoperative AKI. Results: Among the 903 patients included, 326 cases in the low level HDL-C group (36.1%) and 577 cases (63.9%) in the normal level HDL-C group. 351 cases (38.9%) had AKI after cardiac surgery with CPB, of which 156 cases (47.9%) in the low level HDL-C group and 195 cases (33.8%) in the normal level HDL-C group, and the difference was statistically significant (P<0.001). Compared with the normal level HDL-C group, the incidence of postoperative AKI in the low level HDL-C group was higher (P<0.001), and the ventilator use time, the duration of ICU and the length of stay were prolonged (P<0.001). After adjusted for age, gender, comorbidities (hypertension, diabetes), anemia, hyperuricemia, hypoalbuminemia, proteinuria, preoperative renal function, preoperative cardiac function, preoperative coronary angiography, cardiopulmonary bypass time, aortic clamping time, type of cardiac surgery, postoperative hypotension and other influencing factors, binary Logistic regression analysis showed that preoperative low level HDL-C was an independent risk factor for AKI in patients after cardiac surgery with CPB (OR=1.413，95%CI 1.023~1.950，P=0.036). Conclusion: AKI is a common complication after cardiac surgery with CPB, and identify preoperative low HDL-C is an independent risk factor for AKI.