Objective: To learn the interaction of serum direct bilirubin and blood lipids on the risk of carotid atherosclerosis and carotid plaque. Methods : The subjects were selected from Hangzhou Wuyunshan Sanatorium from March 2016 to December 2018. Demographic information,laboratory testing results and carotid intima-media thickness（IMT）were collected. The logistic regression model was employed for the association of direct bilirubin,blood lipids and their interaction with the risk of carotid atherosclerosis and carotid plaque. Results: Totally 8 308 subjects were recruited. Among them,616（7.41%） subjects had carotid atherosclerosis,and 2 409（29.00%）subjects had plaques. The results of multivariate and multinomial logistic regression analysis showed that high level of direct bilirubin was associated with decreased risks of carotid atherosclerosis（OR=0.701,95%CI：0.537-0.916）and carotid plaque（OR=0.647,95%CI：0.527-0.795）;high TC level（OR=1.335,95% CI：1.106-1.611）, high LDL-C level（OR=1.338,95%CI：1.098-1.629）and low HDL-C level（OR=1.431,95%CI：1.148-1.783）were associated with increased risks of carotid atherosclerosis;high TC level（OR=1.325,95% CI：1.151-1.525）and high LDL-C（OR=1.311,95%CI：1.130-1.520）were associated with increased risks of carotid plaque. There were interactions between direct bilirubin and TC or LDL-C on the risk of carotid plaque（P<0.05）. Compared with the subjects with high level of direct bilirubin and normal level of TC,the subjects with normal level of direct bilirubin and high level of TC had significantly higher risk of carotid plaque（OR=1.831,95%CI：1.438-2.333）;compared with the subjects with high level of direct bilirubin and normal level of LDL-C,the subjects with normal level of direct bilirubin and high level of LDL-C had significantly higher risk of carotid plaque（OR=1.814,95%CI：1.427-2.306）. Conclusion The interactions between direct bilirubin and TC or LDL-C increase the risk of carotid plaque. It is important to strengthen blood lipid control in the patients with normal level of direct bilirubin and hyperlipidemia.