Background: Among millions of people who suffer from schistosomiasis in China, adolescents are at increased risk to be infected. However, there is a lack of theory-guided behavioral prevention intervention programs to protect these adolescents. This study attempted to apply the Protection Motivation Theory (PMT) in predicting intentions to engage in protective behaviors against schistosomiasis infection. Methods: The participants were selected using the stratified cluster sampling method. Survey data were collected using anonymous self-reported questionnaire. The advanced structural equation modeling (SEM) method was utilized to assess the complex relationship among schistosomiasis knowledge, previous risk exposure and protective measures in predicting intentions to engage in protective behavior through the PMT constructs. Principal Findings: Approximately 70% of participants reported they were always aware of schistosomiasis before exposure to water with endemic schistosomiasis, 6% of the participants reported frequency of weekly or monthly prior exposure to snail-conditioned water. 74% of participants reported having always engaged in protective behaviors in the past three months. Approximately 7% were unlikely or very unlikely to avoid contact with snail-conditioned water, and to use protective behaviors before exposure. Results from SEM analysis indicated that both schistosomiasis knowledge and prior exposure to schistosomiasis were indirectly related to behavior intentions through intrinsic rewards and self-efficacy; prior protective behaviors were indirectly related to behavior intentions through severity, intrinsic rewards and self-efficacy, while awareness had an indirect relationship with behavior intentions through self-efficacy. Among the seven PMT constructs, severity, intrinsic rewards and self-efficacy were significantly associated with behavior intentions. Conclusions: The PMT can be used to predict the intention to engage in protective behaviors against schistosomiasis. Schistosomiasis intervention programs should focus on the severity, intrinsic rewards and self-efficacy of protection motivation, and also increase the awareness of infection, and enrich the contents of schistosomiasis education.