Selenium-containing phycocyanin (Se–PC) was purified from Se-enriched cultures of a nitrogen-fixing cyanobacterium (Nostoc sp.) using fast protein liquid chromatography. Ammonium sulfate precipitation, DEAE-Sepharose ion-exchange chromatography, and Sephacry S-300 size exclusion chromatography were employed in the process of protein purification. The purity ratio and the separation factor of the purified Se–PC were found to be 5.97 and 14.73, respectively. The Se content in the Se–PC was 550 μg g⁻¹ protein as determined by ICP-AES analysis. Interestingly, we also found that, Se–PC could effectively suppress the paraquat (PQ)-induced cell death and morphological changes, reverse PQ-induced DNA fragmentation and nuclear condensation, and block PQ-induced cell apoptosis through inhibition of superoxide overproduction in human kidney HK-2 cells. The results indicate that Se–PC is a promising selenium species for the protection of renal cells from paraquat-induced damage.