Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979-1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication.