© 2019 The Author(s). Purpose: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-α –308 G>A (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-α –308 G>A gene polymorphism with CRC risk. Methods: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association. Results: The pooled analysis indicated no risk associated with TNF-α –308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863–1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688–2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843–1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849–1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686–2.033). Subgroup analysis revealed that TNF-α –308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias. Conclusions: No association of TNF-α –308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α –308 G>A SNP in the etiology of CRC and to endorse the present findings.