To explore the adaptability of Strongylocentrotus intermedius to different salinity stresses and its oxidative immune regulation mechanism, eight salinity concentration gradients (20‰, 22.5‰, 25‰, 27.5‰, 30‰, 32.5‰, 35‰, 37.5‰) were set based on the hemolymph lethal concentration of sea urchins for 196 hours of chronic stress. The activities of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) content, lysozyme (LZM) activity, and peroxidase (POD) activity in the coelomic fluid of sea urchins were determined at 0, 48, 96, 144, and 196 hours. The results showed that the optimal salinity range was 27.5‰ – 32.5‰. Beyond this range (≤ 25‰ or ≥ 35‰), the activities of the antioxidant enzyme system (SOD, CAT, POD) were significantly inhibited (P < 0.01), and the accumulation peak of malondialdehyde (MDA) was triggered, and the activity of immune defense substances (LZM) weakened. Based on the results of this experiment, it is proposed that the fluctuation of salinity in aquaculture should be controlled within ± 2.5‰, providing a theoretical basis for the breeding and culture of sea urchins.