To study the effectiveness of comprehensive control measures based on systematic ecological system construction to interrupt the transmission of schistosomiasis in hilly endemic regions in Sichuan Province, so as to provide the evidence for adjustment of schistosomiasis prevention and control strategies. A high endemic area of schistosomiasis, Panao Township of Dongpo District in Meishan City, was selected as a demonstration area. The comprehensive measures for schistosomiasis control with focus on systematic ecological management were implemented, and the income of residents, indexes of schistosomiasis control effect and so on were investigated before and after the intervention and the results were compared. The project based on systematic ecological system construction started in 2009 and 317.351 million Yuan was put into the construction. The construction included economic forest plant base (1 866.68 hm2, 72.66% of the total farmland areas), ecological protection gardens (585.35 hm2) and so on. Totally 97.04% of historical areas with Oncomelania hupensis snails were comprehensively improved. In 2015, the peasants´ pure income per capita increased 4 938 Yuan, with the average annual growth rate of 14.69%. All the farm cattle were replaced by the machine. The benefit rate of water improvement was increased by 52.84% and the coverage rate of harmless toilets increased by 18.30%. The positive rate of serological tests for schistosomiasis decreased from 7.69% to 3.50%, and the positive rate of parasitological tests decreased from 1.18% to 0. The area with snails was decreased from 23.33 hm2 to 0. The awareness rate of schistosomiasis control knowledge and correct behavior rate of the residents increased from 85.50% and 82.60% to 95.70% and 93.90% respectively. The comprehensive schistosomiasis control measures based on systematic ecological management are conform to the currently actual schistosomiasis prevention and control work in hilly endemic regions, and have good ecological economic benefit and schistosomiasis control effectiveness, which provide an effectively new model of prevention and control for advancing process, consolidating the effect, finally realizing goal of interruption and elimination of schistosomiasis in hilly endemic regions.