Aquaculture is one of the important ways to utilize alkali-saline water or land effectively. It is important to clarify the physiological and molecular mechanisms of fish alkali-saline adaptation, which is the prerequisite to breed new varieties for aquaculture in alkali-saline water with middle or high alkalinity. This paper summarized the advances of research of physiological and molecular mechanisms in several representative fish species inhabiting alkali-saline lakes around the world, including tissues micro-changing, plasma iono-osmoregulation, ammonia nitrogn metabolism, acid-base regulation, hormone regulation and genome adaptations. Based on these latest advances, we consider that the alkali-saline tolerant fish have evolved characteristics of strong phenotypic plasticity, complexity and integrity due to living in extreme hypersaline-alkali habitats for a long time. It is suggested that the research of correlation exploration should be extended to the determination of causality at gene level, through systematically integrating the information of physiology, phenotype, behavior and various omics, which will promote the research of the mechanisms of alkali-saline adaptation molecularly and evolutionarily for alkali-saline tolerant fish in the future.