Summary Background Some studies have suggested that human HLA status might potentiate development of keloids phenotype, and exists ethnic differences. No report has been published about HLA-DQA1 and DQB1 alleles associated with keloids in Chinese Hans. Objectives To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to keloids in Chinese Hans. Methods Polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles among 192 patients with keloids and 273 healthy controls in Chinese Hans. Results (1) The frequencies of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 (OR = 2.13, P c = 0.0063; OR = 14.42, P c −7 and OR = 6.09, P c −7 , respectively) were significantly higher, while the frequencies of DQA1*0501, DQB1*0201 and DQB1*0402 (OR = 0.46, P c = 0.0099; OR = 0.24, P c −4 and OR = 0.10, P c = 0.0054, respectively) were lower in patients than in controls. (2) In this study significant susceptibility haplotypes to keloids were DQA1*0104–DQB1*0501 and DQA1*0104–DQB1*0503. (3) HLA-DQB1*0501 and DQB1*0503 were positively associated with all subgroups of keloid patients. However, the DQA1*0104 (OR = 2.51, P c = 0.0009; OR = 2.22, P c = 0.0090 and OR = 2.20, P c = 0.0117, respectively) was only prevalent in keloid patients with single site, moderate severity and negative family history. (4) HLA-DQB1*0201 (OR = 0.27, P c = 0.0018 and OR = 0.27, P c = 0.0012, respectively) and DQB1*0402 (OR = 0.07, P c = 0.0270 and OR = 0.07, P c = 0.0306, respectively) were negatively associated with moderate severity and negative family history in keloids, moreover, HLA-DQB1*0201 (OR = 0.23, P c = 0.0003) and DQA1*0501 (OR = 0.43, P c = 0.0234) were less prevalent in patients with single site. Conclusion This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with keloids.