Objective: To investigate the correlation between ocular Demodex folliculorum infection and secondary immunodeficiency diseases. Methods: A total of 192 patients with secondary immunodeficiency diseases from Xiamen Branch, Zhongshan Hospital, Fudan University during November 2019 to January 2020 were enrolled, including patients with malignant tumors, chronic kidney disease, diabetes, and autoimmune diseases. Two hundred and forty-six visited patients without secondary immunodeficiency diseases were served as controls. The eye lashes were taken and examined under optical microscope to observe the status of Demodex folliculorum infection. Results: Demodex folliculorum was found in 162 of 192 patients (84.4%) with secondary immunodeficiency diseases and 150 of 246 controls(61.0%)（P<0.05）. Among these subjects, patients with diabetes had the highest infection rate (89.7%). The variable correlation analysis revealed that immunodeficiency diseases was positively correlated with Demodex folliculorum infection(r=0.256, P<0.001). Multivariate Logistic regression analysis showed that the secondary immunodeficiency diseases doubled the risk of ocular Demodex folliculorum infection (OR=2.09, 95%CI 1.25-3.47, P=0.005). Conclusions: Secondary immunodeficiency may be a high-risk factor for the ocular infection with Demodex folliculorum, and attention should be given to Demodex folliculorum examination in diabetes patients.