Tumor necrosis factor-α (TNF-α) has been reported to play a part in the development of obstructive sleep apnea (OSA) and its complications. However, the relationship between TNF-α and OSA still remains inconclusive. We aimed to systematically review and synthesize studies published to date on association between the two in adults.We searched for English-language articles containing original human data from case-control study studies in adults≥18 years of age. The selection criteria were set according to the PICOS framework. Articles were independently reviewed by three investigators. Data regarding demographics, clinical characteristics, and TNF-α levels were obtained. A random-effects model was applied to evaluate the overall effect sizes by calculating standard mean difference (SMD) and its 95% confidence intervals (CIs).Of 393 identified abstracts, 50 articles (3503 OSA patients and 3379 health controls) were ultimately included in this meta-analysis. The results indicated that the TNF-α level in patients with OSA was 1.77 (95%CI, 1.37 to 2.17, I2 = 97.8%, P < 0.0001) times higher than in the control group. Subgroup analyses showed a positive correlation between the level of TNF-α and OSA severity. According to meta-regression, we noted that aging significantly predicted an increased effect size of TNF-α level in OSA patients (P < 0.007).This study identified a significant association between OSA and elevated TNF-α level in adults. Meanwhile, TNF-α levels were consistently correlated with severity of OSA, which indicated it might be a promising biomarker for the development of OSA. However, well-designed, large-scale, case-control cohorts are needed to better understand the relationship of TNF-α in the context of adult OSA.