Aiming at realizing efficient microalgae-based CO2 sequestration from coal-fired power plants, this study investigated the interaction between the mass transfer of SO2-contained flue gas and microalgae growth. The results indicate that the CO2 dissolution in microalgae suspension and the growth of Chlorella vulgaris could be hindered by solution acidification and oxidative molecular species produced in the conversion of bisulfite to sulfate. With the SO2 concentration increased from 0 to 400 ppm, the pH of the culture medium decreased from 7 to 2, and the SO42− concentration reached 1 g L−1, resulting in a decrement of 18.1% in the CO2 dissolution rate. Moreover, the Chlorella cells could only maintain their growth within the SO42− concentration of 800 mg L−1 accompanied by a decrement of 58% in maximum biomass concentration. The cultivation collapsed under excessive SO2 (over 400 ppm) as the plasmolysis and chloroplast decomposition occurred which severely inhibited the microalgal photosynthesis. This work provides a guide to cultivating microalgae using real flue gas.