The protective ozone layer is continually depleting owing to an increase in the levels of solar UV-B radiation, which has harmful effects on organisms. Algae in desert soil can resist UV-B radiation, but most research on the radiation resistance of desert algae has focused on cyanobacteria. In this study, we found that desert green algae, Chlorella sp., could maintain high photosynthetic activity under UV-B stress. To examine the tolerance mechanism of the desert green algae photosystem, we observed the physiological and transcriptome-level responses of Chlorella sp. to high doses of UV-B radiation. The results showed that the reactive oxygen species (ROS) content first increased and then decreased, while the malondialdehyde (MDA) content revealed no notable lipid peroxidation during the UV-B exposure period. These results suggested that Chlorella sp. may have strong system characteristics for scavenging ROS. The antioxidant enzyme system showed efficient alternate coordination, which exhibited a protective effect against enhanced UV-B radiation. DNA damage and the chlorophyll and soluble protein contents had no significant changes in the early irradiation stage; UV-B radiation did not induce extracellular polysaccharides (EPS) synthesis. Transcriptomic data revealed that a strong photosynthetic system, efficient DNA repair, and changes in the expression of genes encoding ribosomal protein (which aid in protein synthesis and improve resistance) are responsible for the high UV-B tolerance characteristics of Chlorella sp. In contrast, EPS synthesis was not the main pathway for UV-B resistance. Our results revealed the potential cell damage repair mechanisms within Chlorella sp. that were associated with high intensity UV-B stress, thereby providing insights into the underlying regulatory adaptations of desert green algae.