Abstract: Objective To detect the expression of piRNA-19166 in esophageal squamous cell carcinoma and analyze its clinicopathological significance. Methods The expression of piRNA-19166 was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(qRT-PCR)in tissues of esophageal squamous carcinoma and their paracancerous normal esophageal tissues of 96 cases, and the relationship between the expression of piRNA-19166 and pathological materials was analyzed. The qRT-PCR was used to detect the expressions of piRNA-19166 in three types of esophageal cancer cells and normal esophageal epithelial cells. Results In the 96 cases of esophageal squamous cell carcinoma, the expression of piRNA-19166 was decreased in 71 cases and was normal or increased in 25 cases. Compared with the paracancerous normal esophageal tissues, the expressions of piRNA-19166 in esophageal cancer cell lines EC9706, TE-1 and ECa10 were relatively low, and the expressions of piRNA-19166 in ECa10 and EC9706 cells were significantly lower than those in the paracancerous normal esophageal tissues(P<0.05 or P<0.01). The results showed that the low expression of piRNA-19166 was significantly correlated with the degree of differentiation, lymph node metastasis and TNM staging(P<0.01). Conclusion The piRNA-19166 may be a new tumor suppressor gene in esophageal cancer, and the low expression of piRNA-19166 promotes the occurrence, development and metastasis of esophageal cancer.