Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) has been recently documented in various malignancies, but its role in non-small cell lung cancer (NSCLC) remains uncertain. In the current study, we investigated the level of TNFAIP8 in NSCLC tissues, adjacent noncancerous lung tissues, healthy lung tissues, CD4+ T cells, and CD8+ T cells by real-time reverse transcription PCR (RT-PCR) and Western blot analysis. Results revealed that the mRNA level of TNFAIP8 was significantly increased in cancer tissue than in healthy lung tissue from donors (p < 0.001). Interestingly, adjacent noncancerous lung tissues also showed higher mRNA level of TNFAIP8 than healthy lung tissue from donors (p < 0.01). Similarly, protein level of TNFAIP8 was elevated in NSCLC tissues and adjacent noncancerous lung tissues. We further analyzed TNFAIP8 expression in CD4+ T cells and CD8+ T cells. Data demonstrated that both mRNA level and protein level were significantly decreased in tumor-infiltrating CD4+ and CD8+ T cells than in peripheral CD4+ and CD8+ T cells. Moreover, patients with advanced stages presented lower protein expression of TNFAIP8 in tumor-infiltrating CD8+ T cells than patients with primary stages (p < 0.05). These results provide evidence that TNFAIP8 plays critical roles in NSCLC and may be used as a therapeutic target for the disease.