Macrobrachium nipponense is a new aquaculture species with high market demand and is preferred as food by Asian consumers. However, its nutrient requirements and optimal dietary sources have not been fully evaluated. In the present study, we examined four common plant protein sources (soybean meal, cottonseed meal, rapeseed meal, and peanut meal) as partial replacement for 25% fishmeal protein in five isonitrogenous and isocaloric diets in M. nipponense for 8 weeks. The nutritional effects of the four plant protein sources were compared by means of growth performance, feed efficiency, histology, biochemical composition, oxidative stress, total hemocyte count, and in vitro digestion. Prawns fed the diets containing soybean (730.96 ± 33.50%) and cottonseed meals (672.32 ± 74.52%) had higher weight gain than those fed on rapeseed (503.71 ± 50.85%) and peanut (507.79 ± 52.10%) meal diets (p < 0.05). Similarly, the feed conversion ratios of prawns fed on soybean (1.66 ± 0.12%) and cottonseed (1.88 ± 0.06%) meal diets were significantly lower than those fed on rapeseed (2.37 ± 0.10%) and peanut (2.77 ± 0.16%) (p < 0.05) meal diets. No significant differences were found among groups in the hepatopancreas and intestinal histological characteristics, activities of antioxidant enzymes, and hemocyte number. The amino acid composition in diets and prawn muscles was comparable among groups. Soybean meal showed the highest in vitro digestibility. Taken together, soybean and cottonseed meals could be good candidates for partial fishmeal replacement in M. nipponense diets.The Construction project of Shanghai Modern Agricultural Technology System for Prawn Industry (No. 2014-5) and Program for New Century Excellent Talents in University