Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that is mainly distributed in the seafood such as fish, shrimps and shellfish throughout the world. V. parahaemolyticus can cause diseases in marine aquaculture, leading to huge economic losses to the aquaculture industry. More importantly, it is also the leading cause of seafood-borne diarrheal disease in humans worldwide. With the development of animal model, next-generation sequencing as well as biochemical and cell biological technologies, deeper understanding of the virulence factors and pathogenic mechanisms of V. parahaemolyticus has been gained. As a globally transmitted pathogen, the pathogenicity of V. parahaemolyticus is closely related to a variety of virulence factors. This article comprehensively reviewed the molecular mechanisms of eight types of virulence factors: hemolysin, type III secretion system, type VI secretion system, adhesion factor, iron uptake system, lipopolysaccharide, protease and outer membrane proteins. This review comprehensively summarized our current understanding of the virulence factors in V. parahaemolyticus, which are potentially new targets for the development of therapeutic and preventive strategies.