Dynamic interaction between tumor cells and the microenvironment is critical for tumorigenesis, and cancer immunosurveillance plays an important role in the tumor evolution. In some tumors (such as esophageal cancer, pancreatic cancer and colorectal cancer), studies have shown that the number of tumor-infiltrating lymphocytes (TILs) has a significant relationship with the prognosis, but there is little research on the prognosis of TILs and non-small cell lung cancer (NSCLC) has been performed. Therefore, it is necessary to discover the relationship between the TILs and cytokines with NSCLC prognosis and metastasis in patients. Tumor samples were carefully examined for tissue preservation and complete follow-up. A total of 107 tumor samples from NSCLC patients with radical surgical resection were enrolled for the analysis. All samples were subjected to immunohisto-chemistry for detection of CD3, CD4, CD8, CD28, forkhead box protein P3 (Foxp3), cytotoxic T lymphocyte-associated protein-4, cyclooxygenase2 (COX-2), transforming growth factor β 1, interleukin-2 (IL-2), interleukin-6, interleukin-10, interleukin-12 receptor and hypoxia inducible factor 1a (HIF-1a). The number, function and location of the targets were analyzed to determine their correlation with disease-free survival (DFS) and overall survival (OS). Immunhistochemical results from 107 samples indicated that the FoxP3+ regulatory TIL (HR = 1.336, P = 0.031), IL-2 (HR = 0.595, P = 0.007) and HIF-1a (HR = 1.510, P = 0.002) levels in tumor cells closely correlated with DFS in a COX analysis model. FoxP3+ regulatory TILs (HR = 1.566, P = 0.002) significantly correlated with OS and tumor node metastasis staging. The patients were divided into two groups due to the coexpression pattern of the IL-2, FoxP3+ and HIF-1a. The high-risk group had an overall worse survival than those at low risk. We confirmed that Foxp3 expression in lymphocyte and IL-2 expression in tumor cells were associated with recurrence or transfer. Furthermore, we also observed that HIF-1a expression significantly correlated with DFS and OS.