Studies on the biological effects of microplastics pollution on aquatic animals mostly focused on the ocean, but the potential effects on freshwater organisms are less known. In this study, the effects of polystyrene （PS） particles with different particle sizes （5 μm, 1 μm, 100 nm） on juvenile Chinese mitten crab （Eriocheir sinensis） were investigated. Hepatopancreas injury index： alanine aminotransferase （ALT）, aspartate aminotransferase （AST）； serum immune index： alkaline phosphatase （AKP）, acid phosphatase （ACP）； Oxidative stress index： malondialdehyde （MDA）, catalase （CAT）； and neurotoxicity index： acetylcholinesterase （AchE） were analyzed. The pathological changes of gills and hepatopancreas were analyzed by hematoxylin-eosin （H.E） staining. The results showed that exposure to microplastics after 7 d, 100 nm group had significantly higher MDA content, CAT activity decreased significantly, the AKP activity of three treatment group were significantly lower, and 1 μm and 100 nm group of ACP activity was significantly reduced. The activities of AST, ALT and AchE gradually decreased with the decrease of particle size and the extension of exposure time. In conclusion, microplastics with different particle sizes caused varying degrees of hepatopancreas injury, oxidative stress and reduced immune capacity in crabs. The toxicity level was ranked as follows： 100 nm > 1 μm > 5 μm, indicating that the particle size was one of the most important factors affecting the health of Chinese mitten crabs. This study provides basic data and theoretical basis for further understanding the toxic effects of microplastics on freshwater crustaceans.