Abstract: In order to investigate the effect of Shewanella sp. fermented cottonseed protein replacing fishmeal on growth performance and non-specific immunity of turbot (Scophthalmus maximus L.), this study was conducted using 50% fish meal group as the control group, and experimental groups with fermented cottonseed protein and cottonseed protein were used as the experimental group replacing 20% of fish meal in the feed. Three kinds of compound feeds with isonitrogenous and isofat (fish meal group, cottonseed protein group, fermented cottonseed protein group) were prepared. Turbot with an initial body weight of (17.52±0.02) g were cultured for 8 weeks. The results showed that the weight gain rate (WGR), specific growth rate (SGR), and protein efficiency (PER) in the fermented cottonseed protein group were significantly higher than those in the cottonseed protein group, and the feed coefficient (FCR) was significantly lower (P<0.05), with no significant difference from the fish meal group. The antioxidant indices revealed that the fermented group had significantly higher total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity in the liver than that in the cottonseed protein group, significantly higher catalase (CAT) activity than that in the fish meal group, and significantly lower malondialdehyde (MAD) content than that in the fish meal group (P<0.05). Histomorphology analysis showed that the intestinal villi height in the fermented group was significantly higher compared to the cottonseed protein group (P<0.05) and not significantly different from the fish meal group. In terms of immunity, the expression of intestinal pro-inflammatory factor genes (il-8, ifnγ, il-1β) and TLR2/NF-κB pathway genes (tlr2, myd88, nf-κb p65) was significantly suppressed in the fermented cottonseed protein group compared with the cottonseed protein group (P<0.05), with no significant difference from the fish meal group. Conversely, the expression of tight junction protein genes (zo-1, occludin, tricelluin) was significantly up-regulated (P<0.05), in which zo-1 and occludin expression was significantly higher than that of fish meal group. Under the present experimental conditions, Shewanella sp. fermentation of cottonseed protein significantly improved the negative effects of cottonseed protein replacing fish meal on the turbot growth and immunity, and could replace 20% of fish meal in turbot feed.