The objective of this study was to explore the relationship between islet autoantibodies of glutamic acid decarboxylase (GADA), islet antigen-2A (IA-2A), insulin autoantibody (IAA), and human leukocyte antigen (HLA)-DQ genotypes in type 1 diabetes (T1D) patients and their first-degree relatives (FDRs). Cross-sectional and case-control study. Four hundred and ninety-five T1D patients, 419 FDRs, and 376 control subjects in Han Chinese populations were recruited and tested for GADA and IA-2A, while 71 cases, all FDRs and 300 controls were tested for IAA. The 338 T1D patients (including 187 antibody-positive and 151 antibody-negative patients), 173 FDRs and 278 controls were genotyped for HLA-DQ with polymerase chain reaction sequencing-based method. Compared with the control, the frequency of DQA103-DQB10303, DQA105-DQB10201, and DQA103-DQB10401 haplotypes was higher (P < 0.05-0.01) but DQA10102-DQB10602 haplotype was lower (P < 0.01) in T1D patients. DQA103 allele was less in the FDRs than in their probands (P < 0.05). GADA was more prevalent in T1D patients carrying DQA105-DQB10201 or DQA103-DQB10401 haplotype (55.8% vs 41.0%, 65.5% vs 40.3%, P < 0.05-0.01), whereas IA-2A presented more in the patients carrying DQA103-DQB10303 haplotype (27.0% vs 7.9%, P < 0.05-0.01), both GADA and IA-2A showed frequently in the patients with DQA103-DQB10303/DQA105-DQB10201 haplotypes (34.5% vs 9.7%, P < 0.01). GADA positivity was lower in the patients with DQA10102-DQB10602 haplotype (16.7% vs 45.9%, P < 0.05). The frequency of IAA was not different between patients with and without susceptible DQ haplotypes (P > 0.05). GADA, IA-2A or IAA presented frequently in FDRs with DQA103-DQB1*0303 haplotype. The findings in the study indicate that some of specific HLA-DQA1/-DQB1 genotypes and haplotypes not only confer susceptibility to T1D but also are associated with the presence of the islet autoantibodies in the Han Chinese population.