Objective To investigate risk factors for the development of advanced schistosomiasis. Methods The case\|control study was designed with a match of 1∶1 and 1∶2. Healthy persons and chronic schistosomiasis patients were used as control. Each group was composed of 213 cases. Items investigated included: history of schistosomiasis and treatment, exposure to the contaminated water, social\|economical condition and nutritional status, other concomitant diseases. Cellular and humoral immunity, HBVMs and ABO blood groups were also detected. Statistical analysis was performed by 1∶1 and 1∶2 matched single and stepwise conditional logistic regression analysis with SAS software. Results By stepwise conditional logistic regression analysis, it was revealed that number of schistosomiasis examination(OR=1\^168-1\^311), interval from first infection to last treatment(OR=1\^142), interval from first infection to this investigation (OR=1\^089), \{HBsAg\++\}(OR=4\^683-10\^759), \{HBcAb\++\} (OR=2\^873), \{HBsAg\++\}+\{HBeAb\++\}+\{HBcAb\++\}(OR=7\^64) were risk factors of developing advanced schistosomiasis. The average living space and cellular immunity were lower in advanced schistosomiasis patients than others. No association was found between advanced schistosomiasis and ABO blood groups. Conclusion The development of advanced schistosomiasis is associated with repeated infections, and delayed or incomplete treatment. Combined infection with hepatitis B, poor socio\|economic conditions and impaired cellular immunity may increase the pathogenetic risk of schistosomiasis.