Among more than 75 variants of microcystin (MC), microcystin-LR (MC-LR) is one of the most common toxins. In this study, the feasibility of using Caenorhabditis elegans to evaluate MC-LR toxicity was studied. C. elegans was treated with MC-LR at different concentrations ranging from 0.1 to 80μg/L. The results showed that MC-LR could reduce lifespan, delay development, lengthen generation time, decrease brood size, suppress locomotion behavior, and decreases hsp-16-2-gfp expression. The endpoints of generation time, brood size, and percentage of the population expressing hsp-16-2-gfp were very sensitive to 1.0μg/L of MC-LR, and would be more useful for the evaluation of MC-LR toxicity. Furthermore, the tissue-specific hsp-16-2-gfp expressions were investigated in MC-LR-exposed animals, and the nervous system and intestine were primarily affected by MC-LR. Therefore, the generation time, brood size, and hsp-16-2-gfp expression in C. elegans can be explored to serve as valuable endpoints for evaluating the potential toxicity from MC-LR exposure.