Advanced esophageal squamous cell carcinoma (ESCC) still has a dismal prognostic outcome. However, the current approaches are unable to evaluate patient survival. Pyroptosis represents a novel programmed cell death type which widely investigated in various disorders and can influence tumor growth, migration, and invasion. Furthermore, few existing studies have used pyroptosis-related genes (PRGs) to construct a model for predicting ESCC survival. Therefore, the present study utilized bioinformatics approaches for analyzing ESCC patient data obtained from the TCGA database to construct the prognostic risk model and applied it to the GSE53625 dataset for validation. There were 12 differentially expressed PRGs in healthy and ESCC tissue samples, among which eight were selected through univariate and LASSO cox regression for constructing the prognostic risk model. According to K-M and ROC curve analyses, our eight-gene model might be useful in predicting ESCC prognostic outcomes. Based on the cell validation analysis, C2, CD14, RTP4, FCER3A, and SLC7A7 were expressed higher in KYSE410 and KYSE510 than in normal cells (HET-1A). Hence, ESCC patient prognostic outcomes can be assessed by our PRGs-based risk model. Further, these PRGs may also serve as therapeutic targets.