Perfluorooctanoic acid (PFOA) has been found to distribute and accumulate widely in the environment. In this study, the acute toxicity, behavioral activity, regeneration, antioxidant enzyme activities, and cell apoptosis effects of PFOA on planarian Dugesia japonica have been investigated. The results show that the mortality is directly proportional to the PFOA concentration, and planarian locomotor velocity (pLMV) is significantly reduced with increasing both the exposure time and PFOA concentration. The recovery of the motility for planarians pre-treated with PFOA is found to be time- and dose-dependent, and all planarians recover their motility completely after 72 hr. The appearance of auricles in regenerating animals is more easily affected by PFOA exposure in comparison to the appearance of eyespot. The SOD activities and CAT activities are changed in the PFOA-exposed planarians. Increasing PFOA exposure time or concentration can cause an obvious increase of apoptosis in the brain, eye, and parenchyma region. The results suggest that PFOA is much more toxic for inducing oxidative stress, cell apoptosis, and development toxicity in planarians.