Despite the importance of behavioural and environmental risk factors, there are arguments consistent with the existence of a genetic susceptibility to human African trypanosomiasis (HAT). A candidate gene association study was conducted in the Democratic Republic of Congo using a family-based sample which included a total of 353 subjects (86 trios; one case and parents (n=258) and 23 families with more than one case and parents (n=95)). Polymorphisms located on the IL1alpha, IL4, IL6, IL8, IL10, TNFalpha and IFNgamma genes were genotyped after re-sequencing of the genes for extensive SNP search. The T allele of the IL6(4339) SNP was significantly associated with a decreased risk of developing the disease (p=0.0006) and a suggestive association was observed for the IL1alpha(5417 T) SNP and an increased risk of developing the disease. These results suggest that genetic variability of the IL6 and to a lesser extent the IL1alpha gene are involved in the development of HAT. For the TNFalpha and IL10 gene polymorphisms, association results obtained here were different from those we observed in another population living under different epidemiologic conditions. This underlines the complexity of the interactions existing between host genetic polymorphisms, parasite diversity and behavioural and environmental risk factors in HAT.