Abstract: Objective: To conduct a preliminary investigation on the expression of the high-mobility group box-1 (HMGB1) protein, and its relationship to metastasis of the lymph nodes and prognosis of patients with esophageal squa -mous cell carcinoma (ESCC).Methods:Specimens from72cases with complete clinical and follow-up data of thoracic ES -CC were collected. Immunohistochemical and statistical methods were used to observe the expressions of HMGB1 and VEGF-C, VEGF-D, LYVE-1 in ESCC. The relationship among the expression of HMGB1, VEGF-C and VEGF-D, micro-lym -phatic vessel density (MLD), lymphatic metastasis, as well as between the pathological parameters and prognosis of the ESCC patients were analyzed. Results: There was a high expression of HMGB 1 protein in ESCC, and the positive rate of the protein reached 69.44%. However, there was less expression in the normal tissue. The positive rate of HMGB1 expres-sion in the group with lymph node metastasis was significantly higher than in the group without ( 81.82% vs58.97%), with a significant difference between the two (P<0.05). Moreover, the HMGB 1 expression was closely correlated to ESCC staging, expression of VEGF-C and VEGF-D, MLD, as well as the prognosis of the patients ( P<0.05or P<0.01). At the same time, the VEGF-C and VEGF-D expression were also in close relation with the lymphatic metastasis of ESCC and MLD ( P<0.05,P<0.01) Conclusion:In ESCC, the considerable expression of HMGB 1 may promote the lymph- angiogenesis by regulating the expression of VEGF-C and VEGF-D, thus facilitating the lymphatic metastasis and affecting the prognosis. Therefore, HMGB1 may possibly become a major biological marker reflecting the prognosis of ESCC and an important target of an-ti-lymphangiogenesis in treatment.