In this study, we developed a microbiota‐based risk prediction model (MRP model) and an MRP‐plus model (combining tumor stage, tumor size, and MRP model) using 16S rRNA sequencing and droplet digital polymerase chain reaction (ddPCR) testing, validated the feasibility of the risk prediction index and MRP‐plus model for the efficient use of NAT, and predicted the prognosis of patients in clinical cohorts, which could potentially guide therapeutic clinical decision‐making in the treatment of patients with ESCC. The gene discussed is BRD2; the disease is esophageal squamous cell carcinoma.