To examine the correlation between multiple sclerosis (MS) in Chinese Southern Han population and the polymorphism of HLA-DRB1 and -DPB1 alleles, and compare it to the reports of Western, Japanese and Northern Chinese populations.The HLA-DRB1 and -DPB1 alleles of 26 patients with conventional MS (C-MS), 13 patients with optic-spinal form of MS (OS-MS), and 50 normal controls were determined by sequence-based typing (SBT) method. The frequency of the HLA alleles was compared between the 2 MS subtypes and the MS subtypes and the controls by chi(2) or Fisher exact probability test. The P values were corrected according to Bonferroni's method to calculate corrected the P values (Pc).A total of 27 HLA-DRB1 alleles and 13 HLA-DPB1 alleles were identified in the 39 MS patients and 50 controls. The frequencies of DRB1(*)0406 (P = 0.014, OR = 2.09) and DRB1(*)1302 alleles (P = 0.007, OR = 2.84) were higher in the OS-MS patients than in the controls. In addition, the DRB1(*)120201 allele was more frequent in the C-MS patients than in the controls, and the frequency of DPB1(*)2101 was higher in the OS-MS patients than in the controls. However, all the differences were of no significance since the corrected P values (Pc) were all > 0.1. There was no correlation between the MS subtypes and the HLA-DRB1(*)1501 or DPB1(*)0501 as reported in Western and Japanese populations (all P > 0.1).The correlation between HLA-DRB1 and -DPB1 in Southern Han MS population is different from that in the Western, Japanese, and Northern Chinese populations. Southern Han MS patients may be linked to the HLA-DRB1(*)0406, DRB1(*)1302, DRB1(*)120201 and DPB1(*)2101, but not to the HLA-DRB1(*)1501 or DPB1(*)0501 alleles as reported in the above populations.