Objective To investigate whether antihypertensive agent verapamil can inhibit hepatitis C virus (HCV) infection via reducing the expression of thioredoxin-interacting protein (TXNIP) in hepatocytes of the host. Methods Human hepatocellular carcinoma Huh7.5.1 cells were treated with different concentrations of verapamil, and then the mRNA and protein expressions of TXNIP were detected by qPCR and Western blotting, respectively. The HCV infection level of Huh7.5.1 cells was determined 48 h after treatment with verapamil and cell culture-derived HCV (HCVcc). We observed the effect of verapamil on the Huh7.5.1 cells with TXNIP silenced by siRNA after infected by HCVcc. Huh7.5.1 cells were transfected with expression plasmid of enhanced green fluorescent protein (EGFP) controlled by TXNIP promoter (pTXNIP-EGFP), and then the effect of verapamil on transcriptional activity TXNIP promoter was analyzed. Results Compared with the control group, verapamil (100, 200, 400 μmol/L) significantly inhibited TXNIP expression and HCV infection in Huh7.5.1 cells in a dose-dependent manner (P<0.05). Furthermore, verapamil reduced EGFP expression in Huh7.5.1 cells transfected with pTXNIP-EGFP in comparison with the control group (P<0.05). Conclusion Verapamil can inhibit HCV infection via reducing TXNIP expression, which may be associated with the inhibition of TXNIP promotor transcriptional activity.