The aim of this study was to investigate treatment response and hepatic safety of anti-tumor necrosis factor-α therapy among patients with concomitant rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We reviewed the charts of 101 consecutive RA patients who were eligible for anti-TNF-α therapy in the Chiayi Branch of Chang Gung Memorial Hospital. Group A patients were sero-positive for anti-HCV antibodies and had HCV RNA but were negative for hepatitis B surface antigen (HBsAg). Group B (the control group) patients were sero-negative for both anti-HCV antibodies and HBsAg. Response to anti-TNF-α treatment was assessed by calculating disease activity score at 28 joints (DAS28) at baseline and 5, 8, and 11 months after the start of TNF-α antagonist therapy. Percentage change in DAS28 from baseline to month 5 was 21.36 ± 8.01 % in group A and 26.98 ± 10.43 % in group B (p = 0.011). However, there was no obvious difference in treatment response between groups at other time points. Anti-TNF-α therapy was discontinued within 1 year of starting treatment in two subjects in group A and 4 in group B. Response to anti-TNF-α was better in group B than in group A at 5 months, but there was no substantial difference in response at the 1-year evaluation. Although the study sample was small, our results suggest that the safety of anti-TNF-α therapy is similar in RA patients with and without concomitant HCV infection.