The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case–control and cohort studies. In the case–control study, 397 HCC cases from medical centers were compared with 410 community‐based non‐HCC controls. All of them were anti‐HCV‐seropositive, HBsAg‐seronegative with serum HCV RNA levels ≥1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti‐HCV‐seropositive individuals were followed from 1991 to 2008 to assess the long‐term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow‐up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64vs. 55%,p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 × 106IU/mL) than those infected with HCV non‐1b (1.2 × 106IU/mL,p < 0.001). The multivariate‐adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non‐1b was 1.43 (1.02–2.02). After the long‐term follow‐up, the cumulative lifetime (30–80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non‐1b and 1b, respectively (p < 0.001). The multivariate‐adjusted hazard ratio (95% CI) was 1.85 (1.06–3.22) for HCV 1b compared to non‐1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.