The association between eosinophil count and cholelithiasis among people with Clonorchis sinensis infection is still uncertain. We conducted a cross-sectional study to investigate the associations among Clonorchis sinensis infection, eosinophil count and cholelithiasis. The study included 4628 participants from January to December 2018. The levels of eosinophil count were divided into four groups according to the quartiles of eosinophil count. Spearman's rank correlation was performed to assess the association between eosinophil counts and Clonorchis sinensis egg counts. Multiple regression analysis was performed to evaluate the relationships among C. sinensis infection, eosinophil count and cholelithiasis after adjusting for three models. The prevalence of C. sinensis infection was 38.72% (1792/4628), and the prevalence of cholelithiasis was 6.03% (279/4628). The infection rate of C. sinensis was higher in the cholelithiasis group than in the non-cholelithiasis group (63.08% vs. 37.16%, P < 0.001). Significant differences were found among various eosinophil count quartiles for C. sinensis infection, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA) and non-alcoholic fatty liver disease (NAFLD) (all P < 0.001). A significant positive correlation was found between eosinophil count and log-transformed C. sinensis egg count (r = 0.9477, P < 0.001). Multiple logistic regression analysis revealed that light and moderate intensities of C. sinensis infection were associated with cholelithiasis (P < 0.01 and P < 0.001, respectively), and C. sinensis infection with eosinophil count ranging from 0.05 to 0.5 × 109/l were associated with cholelithiasis (P < 0.05). In conclusion, our findings suggest that the light and moderate infections of C. sinensis with eosinophil count ranging from 0.05 to 0.5 × 109/l may be associated with a higher risk of cholelithiasis.