Low-temperature acclimation is recognized as one of the most important methods of improving cold tolerance. The physiological response and immune function of the fish body could be changed through proper low-temperature acclimation. To elucidate the immune-protective mechanisms of various tilapia strains during low-temperature acclimation, four different strains (GIFT tilapia,hybrid tilapia, red tilapia and Aurea tilapia) were reared at 26. Three weeks later, individual tilapia (body weight 50.73 g ± 4.23 g) were selected and low-temperature acclimation experiments performed. Water temperature was decreased from 26 to 8/d. Blood and head kidney of three fish from each tank were sampled at 26, 20, 14 and 8, and the change in serum cortisol (COR) and immunity indices of the head kidney were compared in the four different tilapia strains over the course of the low-temperature acclimation. The results showed that the levels of serum COR in GIFT and red tilapia at 8 were significantly higher than the other strains. The levels of serum complement 3 (C3), complement 4 (C4), immunoglobulin M (IgM) and the level of c-type lysozyme mRNA in head kidney at 8. COR may play an important role in the regulation of immunity activity and higher levels of COR may inhibit immunity in the fish body. Higher levels of serum COR, C4 and IgM and the expression levels of hepcidin antimicrobial peptides-1 (HAMP1) were observed at 8. The levels of serum COR, C4 and IgM, and expression levels of c-type lysozyme in the head kidney of Aurea tilapia were similar at water temperatures of 8 and 26. At the end of the low-temperature acclimation trial, cumulative mortality of the four different tilapia strains was compared at 8for 48 h. Cumulative mortalities for the GIFT and red tilapia strains were 43.3% and 40.0%, respectively, and were higher than for the hybrid and Aurea tilapia strains. The cumulative mortality of Aurea tilapia was lowest (20.0%). The higher IgM levels in serum and c-type lysozyme and HAMP1 mRNA levels in the head kidney may have enhanced the resistance of the hybrid and Aurea tilapia strains to low-temperature stress and improved survival to cold stress.