Aims: To investigation the correlation between gene expression and immune cell infiltration, the overall survival rate in tumor tissues, which may contribute to the therapy and prognosis of small cell lung cancer (SCLC) patients. Background: SCLC is the most aggressive type of lung neoplasms. There is no proper marker for treatment and prediction of prognosis in SCLC. Objectives: Three gene expression profiles of SCLC patients were obtained from The Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between normal lung samples and SCLC lung samples. Methods: Functional enrichment analysis of all DEGs was conducted to explore the linkage between DEGs and tumor immune and SCLC tumorigenesis. The common genes among the 3 groups in Venn diagram and hub genes in protein-protein interaction (PPI) networks were considered as potential key genes in SCLC patients. TIMER (tumor immune estimation resource) database calculation and Kaplan-Meier survival curves were conducted for investigating the association between potential key genes and immune infiltrates prognosis of SCLC patients, respectively. Results: A total of 750 (top 250 from each study) differentially expressed genes (DEGs) were identified. CLDN18 and BRIP1 were significantly related to immune infiltration in the tumor microenvironment. SHCBP1 and KIF23 were the most related to the prognosis in SCLC patients. Conclusion: The present study may provide some potential biomarkers for the therapy and prognosis of SCLC.