Clear-cell renal cell carcinoma (ccRCC) is one of the most common urological cancers. The tumor microenvironment plays an important role in tumor development. The present study was conducted to identify novel immune-related biomarkers. The differentially expressed genes were identified using the ESTIMATE algorithm base on GEO and TCGA databases. The Kaplan-Meier survival curve and univariate and multivariate analyses were performed. The association between ST8SIA1 and the immune system was explored. The gene set enrichment analysis (GSEA) and online databases were used for functional annotation. ST8SIA1 was identified as a potential prognostic gene. Elevated ST8SIA1 was observed in the tumor tissues compared with adjacent normal tissues and associated with higher T stage and advanced TNM stage (all p < 0.05). The mRNA and protein levels of ST8SIA1 in cancer tissues and cells are also upregulated. The Kaplan-Meier survival curve and univariate and multivariate analyses showed that higher expression of ST8SIA1 was associated with worse OS (all p < 0.05). ST8SIA1 expression levels were negatively correlated with tumor purity and positively associated with infiltrated immune cells and expression of immune checkpoint genes. Function analysis also revealed that ST8SIA1 was significantly associated with immune-related pathways. In conclusion, ST8SIA1 was identified as an immune-related gene and a potential target in ccRCC patients. Further relevant studies are required to validate our findings.Copyright © 2022 Hu, Yang, Wang, Ren and Li.