The present study investigated the HLA-DPA1 and -DPB1 allele and haplotype frequencies in the Chinese Han population. A total of 563 families, which have been typed for the purpose of haematopoietic stem cell transplantation, were included, and three-field allelic resolution typing of HLA-DPA1 and -DPB1 of all individuals were defined by the next-generation sequencing method. HLA-DPA1~DPB1 haplotypes were determined by allele segregation within a nuclear family. A total of 9 HLA-DPA1 and 39 HLA-DPB1 alleles, and 62 HLA-DPA1~DPB1 haplotypes were identified. The three most frequent alleles at HLA-DPA1 locus are HLA-DPA1*02:02:02 (46.581%), HLA-DPA1*01:03:01 (36.456%) and HLA-DPA1*02:01:01 (12.167%); and the three most frequent HLA-DPB1 alleles are HLA-DPB1*05:01:01 (34.014%), HLA-DPB1*02:01:02 (18.428%) and HLA-DPB1*04:01:01 (10.124%). The three most frequent haplotypes are HLA-DPA1*02:02:02~DPB1*05:01:01 (32.327%), HLA-DPA1*01:03:01 ~ DPB1*02:01:02 (14.654%) and HLA-DPA1*01:03:01~DPB1*04:01:01 (9.458%). The HLA-DPA1*02:01~DPB1*02:02 and HLA-DPA1*04:01~DPB1*05:01 haplotypes appear to be unique in Han Chinese. Strong global linkage disequilibrium (LD) between HLA-DPA1 and -DPB1 was confirmed (D′ = 0.848, Wn = 0.684). Moreover, the haplotype frequencies based on the family study were compared with the frequencies estimated by the expectation–maximisation algorithm, and the equivalent results were obtained except for haplotypes with very low frequencies. Our data provide a solid base for HLA-DP dimer association studies and useful information for transplantation and disease association studies.