<p>Green microalgae exhibit varying toxic effects to cadmium (Cd) and some are highly sensitive and tolerant; however, their molecular genomic response to Cd has not been sufficiently elucidated. In the present study, we evaluated genome-scaled responses of the freshwater alga <i>Closterium acutum</i> exposed to Cd, focusing on the genes involved in photosynthesis, antioxidant metabolism, and cell cycle. Treatments with low Cd doses had little effect on cell growth, whereas dosages more than 5.0&#xa0;mg L⁻¹ caused a significant reduction. The median effective concentration (EC₅₀) was calculated to be 0.427 mg L⁻¹. In addition, 140,025 transcriptome contigs were constructed from the <i>C. acutum</i> exposed to different concentrations of Cd. The number of differentially expressed genes (DEGs) increased by Cd treatments in a dose-dependent manner. Gene ontology (GO) analysis showed that photosynthesis related genes were significantly enriched in response to Cd exposure. In particular, light-harvesting chlorophyll <i>a/b</i> binding (<i>Lhc</i>) genes considerably responded to Cd, with an increase of the chlorophyll contents. However, other physiological parameters, such as photosynthetic indices and ROS, showed little change. These findings&#xa0;suggest that <i>C. acutum</i> is very tolerant to Cd, and photosynthetic genes may be partly involved in the molecular response to the heavy metal.</p>