In this study, the physiological and biochemical responses of the freshwater microalgae Synechocystis sp. PCC 6803 to HgCl2 were compared and evaluated using 96 h growth tests in a batch-culture system. The results showed that HgCl2 had a significant inhibition on the growth and Chl a concentration of Synechocystis sp. PCC 6803. Moreover, remarkable physiological and biochemical responses also occurred when the microalgae were exposed to HgCl2. The general increase in MDA content suggests that the toxic effects of metals were probably exerted through free radical generation; and the increase in SOD activity may be viewed as an active defense against metal stress by stimulating the synthesis of proteins against stress and quenching of free radicals. These observations suggest that HgCl2 is toxic to Synechocystis sp. PCC 6803, and its use should be moderately restricted.