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Objective: To investigate the economic burden of hepatitis C patients and related factors in Guangdong province. Methods: In this study, cluster sampling method was used to select cases, including acute hepatitis C, chronic hepatitis C and liver cirrhosis cases from eligible outpatients and inpatients in 1 or 2 large general hospitals in all the 21 cities in Guangdong province. Questionnaire survey was conducted for all the hepatitis C patients to analyze their economic burden, while multivariate linear regression model was used to identify the related influencing factors. Results: A total of 356 hepatitis C patients were enrolled in the study, with 176 outpatients (49.4 % ) and 180 inpatients (50.6 % ) respectively. The average age of the study subjects was (44.79±11.73) year-olds. The annual direct economic costs of patients with acute hepatitis C, chronic hepatitis C and liver cirrhosis were 10 703.22 ( IQR : 7 396.75-16 891.91), 14 886.63 ( IQR : 7 274.00-30 228.25) and 28 874.00 ( IQR : 13 093.69-56 350.00) Yuan (RMB) respectively. The annual indirect costs appeared as 2 426.99 ( IQR : 1 912.18-7 354.52), 3 235.99 ( IQR : 1 323.81-6 619.07) and 5 442.35 ( IQR : 3 235.99-10 296.33) Yuan (RMB) respectively. The annual intangible costs were 5 000.00 ( IQR :2 000.00-10 000.00), 10 000.00 ( IQR : 4 000.00-30 000.00) and 10 000.00 ( IQR : 3 000.00-100 000.00) Yuan (RMB) respectively. The annual total costs were 22 306.17 ( IQR : 14 581.24-50 569.17), 38 050.33 ( IQR : 17 449.57-68 319.62) and 80 152.18 ( IQR : 40 856.09-228 460.79) Yuan (RMB) respectively. Results from the multiple linear regression analysis showed that factors as: annual hospitalization days, annual number of outpatient visits, annual number of hospitalization, type of disease and the levels of the hospitals were related to the economic burden of patients with hepatitis C. Conclusion: Patients with HCV-related diseases presented serious economic problem which calls for close attention in Guangdong province.