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Background: Schistosomiasis japonica remains an important public health concern due to its potential to cause severe outcomes and long-term sequelae. An integrated control strategy implemented in the Peoples' Republic of China has been shown to be effective to control or interrupt the transmission of schistosomiasis. The objective of this study is to estimate the disease burden of schistosomiasis and assess the cost-effectiveness of the integrated control strategy focused on different major interventions at three stages for schistosomiasis control in a lake setting, to provide reference for policy making or planning. Methods: Annual cost data of schistosomiasis control during 2009–2019 were obtained from the control program implementers in Jiangling County, Hubei Province, China. Economic costs are provided in constant 2009 Chinese Yuan (CNY). Epidemiological data of schistosomiasis were collected from the Jiangling county station for schistosomiasis control. Disease burden of schistosomiasis was assessed by calculating years of life lost (YLLs) owing to premature death, years lived with disability (YLDs) and disability-adjusted life years (DALYs). DALYs were calculated as the sum of YLLs and YLDs. We then conducted a rudimentary cost-effectiveness analysis by determining the ratio by dividing the difference between the average cost of integrated control strategy at transmission control (2013–2016) or transmission interruption (2017–2019) and the average cost at stage of infection control (2009–2012) with the difference between the DALYs of schistosomiasis at different control stages. Descriptive statistics on the costs and DALYs were used in the analysis. Results: The total economic costs for schistosomiasis control in Jiangling County from 2009 to 2019 were approximately CNY 606.88 million. The average annual economic costs for schistosomiasis prevention and control at stages of infection control (2009–2012), transmission control (2013–2016), and transmission interruption (2017–2019) were approximately CNY 41.98 million, CNY 90.19 million and CNY 26.06 million respectively. The overall disease burden caused by schistosomiasis presented a downward trend. Meanwhile, the disease burden of advanced cases showed an upward trend with the DALY increased from 943.72 to 1031.59 person-years. Most disease burden occurred in the age group over 45 years old (especially the elderly over 60 years old). Taking the infection control stage as the control, the incremental cost-effectiveness ratio of integrated control strategy was CNY 8505.5 per case averted, CNY 60 131.6 per DALY decreased at transmission control stage and CNY −2217.6 per case averted, CNY −18 116.0 per DALY decreased at transmission interruption stage. Conclusions: The disease burden of schistosomiasis decreased significantly with the implementation of the integrated prevention and control strategy. Surveillance and management on elder population should be strengthened to decrease diseases burden. There remains a need for well-conducted studies that examine the long-term cost-effectiveness of the integrated control strategy for schistosomiasis. Graphic Abstarct: [ABSTRACT FROM AUTHOR]