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Carbon dioxide and other greenhouse gas emissions leads to global warming. Biological capture through microalgae is a potential approach for solving this environmental problem. It is still a technical challenge to enhance the tolerance of microalgae to flue gas if CO2 is fixed from flue gas directly. A new strain, Chlorella sp. Cv was obtained through adaptive evolution (46 cycles) against simulated flue gas (10% CO2, 200 ppm NOx and 100 ppm SOx). It was confirmed that Chlorella sp. Cv could tolerate simulated flue gas conditions and the maximum CO2 fixation rate was 1.2 g L-1 d(-1). In a two-stage process, the biomass concentration was 2.7 g L-1 and the carbohydrate content was 68.4%. Comparative transcriptomic analysis was performed for Chlorella sp. Cv under simulated flue gas and control conditions (10% CO2). These responses against simulated flue gas uncovered the significant difference between the evolved strain and the original strain. The metabolic responses to flue gas were explored with focus on various specific genes. Upregulation of several genes related to photosynthesis, oxidative phosphorylation, CO2 fixation, sulfur metabolism and nitrogen metabolism was beneficial for the evolved strain to tolerate the simulated flue gas. The upregulation of genes related to extracellular sulfur transport and nitrate reductase was essential to utilize the sulfate and nitrate from dissolved SOx and NOx. The results in this study are helpful to establish a new process for CO2 capture directly from industrial flue gas. (C) 2018 Elsevier B.V. All rights reserved.