The lung of yak is an important adaptive organ in the cold and low oxygen environment. Hypoxia can induce the pathological manifestations of pulmonary fibrosis in yak, but there was no study on hypoxia induced pulmonary fibrosis in yak. In this study, lable-free proteomics was used to conduct studies on normal and fibrotic lung tissues of yaks. The results showed that RASSF4, EDC4, CTSC and FECH were significantly up-regulated differential proteins, while CYP27A1, FKBP9, RAD23A and PLSCR2 were significantly down-regulated differential proteins. These findings provided a scientific basis for formulating effective prevention and control strategies, contributing to safeguarding yak health and the sustainable development of plateau animal husbandry, and providing strong support for animal health management and disease prevention and control in plateau areas.