Based on the hypothesis that tumour cells expressing HLA-DR antigen would easily be damaged by the local immune response during preoperative treatments, the relationship was investigated between the expression of HLA-DR antigen in the oesophageal cancer and the effectiveness of the preoperative treatment. Immunohistochemical staining for the detection of HLA-DR antigen in cancer cells from biopsy specimens obtained before undergoing preoperative hyperthermo-chemo-radiotherapy (HCR therapy) in patients with oesophageal squamous cell carcinoma was performed, and the relationship between the expression of HLA-DR antigen and the effectiveness of HCR therapy was evaluated according to a histopathologic examination of resected specimen. A total of 35 cases were examined in which 14 showed strongly positive staining (+2), 14 weakly positive staining (+) and seven negative staining (-). No significant differences in the clinicopathologic factors between the groups were observed. In the 14 strongly positive HLA-DR antigen cases, nine were markedly effective (grade 3) (64.3%), four were moderately effective (grade 2) (28.6%) and one was slightly effective or ineffective (grade 1, 0) (7.1%). In the 14 weakly positive HLA-DR antigen cases, the markedly, moderately and slightly or ineffective cases numbered four (28.6%), eight (57.1%) and two (14.3%), respectively. On the other hand, in the seven patients showing no HLA-DR expression, the markedly, moderately and slightly effective cases numbered one (14.3%), two (28.6%) and four (57.1%), respectively. A statistical difference was observed between the cases of strongly positive and negative staining for HLA-DR antigen (p < 0.05). The expression of HLA-DR antigen in oesophageal cancer cells is thus considered to potentially be a valuable factor for predicting the effectiveness of preoperative treatment.