Abstract: 【Objective】 The aim of this study was to explore the regulatory mechanism of tilapia gill tissue damage under low temperature stress and provide theoretical basis for the subsequent overwintering of tilapia. 【Method】 Tilapia was subjected to 12 ℃ outdoor low temperature stress and 18 ℃ indoor rewarming experiments，with the eurythermal grass carp as reference. The gill tissues of tilapia and grass carp were collected，and tissue sections were made，antioxidant enzyme activities were determined，and real-time fluorescence quantitative PCR was used to detect the expression of immune related genes. 【Result】 When the temperature dropped from 18 ℃ to 12 ℃，the gill tissue of tilapia was severely damaged，which was manifested by aggravated apoptosis，incomplete secondary gill lamellae，fused lamellae，increased interlamellar cell clusters，vacuolation in the tissue，and more blood cell accumulation；after rewarming to 18 ℃，the degree of apoptosis in the gill tissue of tilapia was alleviated，but the lamellae fusion phenomenon did not improve. Under low temperature stress of 12 ℃，the epithelial tissue of the gill filaments of grass carp was slightly thickened，but the secondary gill lamellae and gill lamellae were relatively intact，and the number of apoptotic cells was much less than that of tilapia；after rewarming to 18 ℃，the secondary gill lamellae structure damage of grass carp improved，the thickness of epithelial tissue of gill filament decreased，and the number of apoptotic cells decreased greatly. Under low temperature stress of 12 ℃，the activities of superoxide dismutase（SOD）and catalase（CAT）in the gill tissue of tilapia increased extremely significantly（P<0.01，the same below），while the activity of glutathione peroxidase（GSH-Px）decreased significantly；grass carp showed an extremely significant increase in CAT activity，a significant increase in GSH-Px activity （P<0.05，the same below），and no significant change in SOD activity（P>0.05，the same below）. In addition，the relative expression of BPI，MKK6，STAT1，CD122 and IL-2 genes in tilapia showed extremely significant down-regulation trend under 12 ℃ low temperature stress，while the relative expression of IL-1β gene showed extremely significant upregulation trend；while the relative expression of STAT1 and IL-1β genes in grass carp showed extremely significant upregulation under 12 ℃ low temperature stress，and the relative expression of CD122 and IL-2 genes up-regulated significantly，and the relative expression of BPI and MKK6 genes showed a down-regulation trend，but the difference was not significant. 【Conclusion】 Under low temperature stress，the interaction between oxidative stress，apoptosis and impaired immune function may jointly mediate the damage of tilapia gill tissue，and the damage is irreversible. In the future work on cold resistance of tilapia，molecular marker-assisted selection technology can be used to accelerate the breeding of cold resistant breeds（lines）with cold resistant related genes as molecular markers.