Abstract Background A growing body of evidence suggests that pyroptosis-related lncRNAs (PRncRNAs) are associated with the prognoses of tumor patients and their tumor immune microenvironments. However, the function of PRlncRNAs in lung squamous cell carcinoma (LUSC) remains unclear. Methods We downloaded the transcriptome and clinical information of 551 LUSC samples from the The Cancer Genome Atlas (TCGA) database and randomly separated patients with complete information into two cohorts. Based on the training cohort, we developed a pyroptosis-related signature. We then examined the signature in the test cohort and all retained patients. We also clustered two risk groups in each cohort according to the signature and performed survival analysis, functional analysis, tumor immune microenvironment analysis and drug sensitivity analysis. Results A prognostic signature containing five PRlncRNAs (AP001189.1, PICART1, LINC02555, AC010422.4, and AL606469.1) was developed. A principal component analysis (PCA) indicated better differentiation between patients with different risk scores. Kaplan–Meier (K–M) analysis demonstrated poorer survival among patients with higher risk scores (P