【Objective】To analyze the difference of salivary microbiome between patients with esophageal squamous cell carcinoma（ESCC group）and healthy controls（HC group），and to screen out the target bacteria in saliva of patients with esophageal squamous cell carcinoma. 【Methods】 Salivary samples were collected from 50 patients with esophageal squamous cell carcinoma and 40 healthy controls. Total DNA was extracted，16S rDNA V4 region was amplified by PCR，high-throughput sequencing was performed，and sequencing data was subjected to OUT clustering，species annotation and diversity analysis.【Results】Diversity analysis showed difference in the diversity of the salivary microbiome between the ESCC group and the HC group，but P > 0.05. Species analysis showed that the salivary microbiome in the ESCC group was dominated by Neisseria，Fusobacterium，Haemophilus，Prevotella and Porphyromonas，while Neisseria，Haemophilus， Prevotella，Fusobacterium and Veillonella were the top microbiota in the HC group. LEfse analysis showed that the expression of Porphyromonas in the ESCC group was elevated and the result had statistical significance.【Conclusion】Saliva in the patients with esophageal squamous cell carcinoma has characteristic microbiome composition. Compared with the squamous cell carcinoma is significantly increased，and the result is statistically significant(P < 0.05）.