The major histocompatibility Class II alleles of 108 individuals living in an area endemic for schistosomiasis japonica in China were determined to identify possible immunogenetic associations with advanced schistosomiasis. Two alleles, HLA-DRB1*1202 (P = 0.002) and HLA-DQA*0601 (P = 0.001) were strongly associated with resistance to advanced disease. In contrast, HLA-DQB1*05031 (P = 0.02) was associated with susceptibility to advanced schistosomiasis. The remaining alleles showed no association with advanced disease. Allele DRB1*1202 co-occurred with allele DQA1*0601; therefore, their independent protective effects could not be ascertained. In contrast, alleles DQA1*0601 and DQB1*05031 never co-occurred and had opposite and significant effects on the occurrence of disease.