Accumulating evidence demonstrated that FOXD1 dysregulation was correlated with a broad spectrum of malignancies. However, litter is known about the role of FOXD1 in the progression of lung squamous cell carcinoma (LUSC). We conducted the comprehensive bioinformatics analysis to investigate FOXD1 expression in LUSC from TCGA and GEO datasets, and validated the FOXD1 expression pattern in clinical samples using immunohistochemistry method. ESTIMATE and CIBERSORT algorithms were performed to assess the relationship of FOXD1 and tumor microenvironment and immune cell infiltration. Our study showed that FOXD1 expression was significantly upregulated in LUSC tissues in TCGA dataset, validated by GEO datasets and clinical samples. In TCGA dataset, Kaplan-Meier curves showed that high FOXD1 expression was significantly correlated with favorable prognosis in LUSC patients. Moreover, FOXD1 expression has an impact on immune score and the proportions of immune cell infiltration subgroups. Finally, we predicted FOXD1 may be involved in many immune-related biological functions and cancer-related signaling pathways. Taken together, FOXD1 was upregulated in LUSC tissues, and FOXD1 expression could be a potential prognostic marker. FOXD1 might be associated with tumor microenvironment and perhaps a potential target in the tumor immunotherapy.