Objective To investigate the expression and clinical significance of UL16 binding protein 3 (ULBP3) in human esophageal squamous cell carcinoma (ESCC) and its correlation with nature killer (NK) cells.Methods The relative expression of ULBP3 in the ESCC tissues and corresponding carcinoma adjacent tissues of 40 patients was detected by realtime-poly merase chain reaction (PCR),immunohistochemical staining and Western blot methods.The percentage of NK cells in peripheral blood of same patients was examined by flow cytometry.The correlation between ULBP3 and the percentage of NK cells was analyzed with Pearson method.Results The expression of ULBP3 at mRNA level in the tumor tissues ([4.96 ±-6.11]×10-3) was significantly higher than that of corresponding carcinoma adjacent tissues ([1.64 ± 2.96]× 10-3,t =3.656,P＜ 0.01).The immunohistochemical staining results indicated that the positive rate of ULBP3 in the tumor tissues was 60％ (24/40),however that of corresponding carcinoma adjacent tissues was only 32.5％(13/40,t=3.921,P＜0.01).The Western blot results indicated that the expression of ULBP3 at protein level in the tumor tissues was significantly higher than that in the corresponding carcinoma adjacent tissues.The relative expresssion ULBP3 at mRNA level in carcinoma tissues of ESCC patients with lymph node metastasis and at TNM stage Ⅲ was higher than that of ESCC patients without metastasis and at TNM stage Ⅰand Ⅱ (t=4.839,4.192,P＜0.05).There was no significant correlation between the expression and ages,gender,location of tumors and the differentiation degree of tumor (P＞0.05).At early and mid stage of the tumor,the expression of ULBP3 at mRNA level was positively correlated with the percentage of NK cells in peripheral blood (r=0.5233,P＜0.05),however there was no correlation at advanced stage.Conclusion ULBP3 was highly expressed in ESCC and may be involved in the immune regulation of NK cells.