Pathogens have evolved sophisticated mechanisms to survive oxidative stresses imposed by host defense systems, and the mechanisms are closely linked to their virulence. In the present study, ahpC1, a homologue of Escherichia coli ahpC encoding a peroxiredoxin, was identified among the Vibrio vulnificus genes specifically induced by exposure to $H_2O_2$. In order to analyze the role of AhpC1 in the pathogenesis of V. vulnificus, a mutant, in which the ahpC1 gene was disrupted, was constructed by allelic exchanges. The ahpC1 mutant was hypersusceptable to killing by reactive oxygen species (ROS) such as $H_2O_2$ and t-BOOH, which is one of the most commonly used hydroperoxides in vitro. The purified AhpC1 reduced $H_2O_2$ in the presence of AhpF and NADH as a hydrogen donor, indicating that V. vulnificus AhpC1 is a NADH-dependent peroxiredoxin and constitutes a peroxide reductase system with AhpF. Compared to wild type, the ahpC1 mutant exhibited less cytotoxicity toward INT-407 epithelial cells in vitro and reduced virulence in a mouse model. In addition, the ahpC1 mutant was significantly diminished in growth with INT-407 epithelial cells, reflecting that the ability of the mutant to grow, survive, and persist during infection is also impaired. Consequently, the combined results suggest that AhpC1 and the capability of resistance to oxidative stresses contribute to the virulence of V. vulnificus by assuring growth and survival during infection.