Objective To investigate expression of PD-L1 and its clinical significance in patients with esophageal squamous cell carcinoma (ESCC). Methods Expression of PD-L1 protein in 50 cases of tumor and matched adjacent tissues was identified by immunohistochemical staining and Western blot. Relationship between expression and clinical characteristics was analyzed. Results The positive expression rate of PD-L1 protein was increased in cancer tissue when compared with that in adjacent noncancerous mucosa tissues (42.0 vs 22.0%, P < 0.05). The expression of PD-L1 protein was closely associated with depth of infiltration and TNM stage (P < 0.05). Kaplan-Meier survival analysis in a 30-months follow-up study showed that patients in PD-L1 positively expressed group experienced lower survival rate when compared with those in PD-L1 negatively expressed group (38.1% vs 86.2%, P < 0.05). COX regression analysis result indicated that PD-L1 was the independent prognosis factor of ESCC. Conclusions PD-L1 plays an important role in carcinogenesis of ESCC, PD-L1 may be a potential prognostic and therapeutic target of ESCC.