Provision of chemical modulators has emerged as an effective strategy to govern cell growth and development. Here, the impact of flavonoid quercetin on algal growth, lipid accumulation and transcriptional patterns was investigated in the green microalga Chlorella vulgaris. These results demonstrated that quercetin (15 mu g/l) significantly enhanced the cellular biomass and photosynthetic efficiency, with up to 2.5-fold in the biomass in the stationary phase. Lipidomic analyses revealed that lipid content was increased by 1.8-fold. Furthermore, the functional mechanism of quercetin on the molecular level was dissected by transcriptomic analysis. Results revealed that quercetin upregulated the expression pattern of key genes involved in cellular signaling mechanisms such as phosphatidylinositol 4-kinase alpha, thus consequently enhanced cell growth. Altogether, the data present in this study demonstrate the dramatic role of quercetin on enhancing microalgal biomass and lipid accumulation by unprecedented regulation, of key metabolic nodes, for the first time and provide a novel insight into microalgal metabolism and regulation.