Abstract:[Objective] Chlamydomonas nivalis thrives in polar regions and snowfields of high mountains. C. nivalis is characterized by tolerance to cold and drastic temperature fluctuation. However, the mechanism underlying this tolerance is unknown.[Methods] On the basis of physiological responses of C. nivalis to cyclic temperature fluctuation, we selected 10 sampling times for RNA sequencing. The weighted gene co-expression network analysis (WGCNA) yielded 17 modules, and we picked up 5 modules that were significantly associated with the sample treatment. Then we analyzed the differentially expressed genes under cyclic temperature fluctuation. The selected gene sets were analyzed by functional annotation. [Results] The gene expression on C. nivalis remarkably changed under cyclic temperature fluctuation. Genes coding key enzymes in fructose and mannose metabolism, starch and sucrose metabolism, glutathione metabolism, ascorbate and aldehyde acid metabolism pathways were up-regulated at 4℃. We also found that protein quality control system, photosynthesis system, DNA damage and repair system may play important roles in adaptation to temperature fluctuation. [Conclusion] This study provides important clues to unravel the molecular mechanism of C. nivalis in adaptation to temperature stress and enriches stress-resistant gene resources.