Previous studies have suggested that macrophage migration inhibitory factor (MIF) - 173G/C polymorphism may be associated with cancer risk. However, previous research has demonstrated conflicting results. Therefore, we followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and the meta-analysis on genetic association studies checklist, and performed a meta-analysis to investigate the association between MIF - 173G/C polymorphisms and the risk of cancer. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were combined to measure the association between MIF promoter polymorphisms and cancer risk. The pooled ORs were performed for the dominant model, recessive model, allelic model, homozygote comparison, and heterozygote comparison. The publication bias was examined by Begg's funnel plots and Egger's test. A total of ten studies enrolling 2,203 cases and 2,805 controls met the inclusion criteria. MIF (-173G/C) polymorphism was significantly associated with increased cancer risk under the dominant model (OR = 1.32, 95%, CI = 1.00-1.74, P = 0.01) and the heterozygote comparison (OR = 1.38, CI = 1.01-1.87, P = 0.04). In subgroup analysis, MIF polymorphism and prostate were related to increased risk of prostate and non-solid cancer. In conclusion, MIF polymorphism was significantly associated with cancer risk in heterozygote comparison. The MIF -173G/C polymorphism may be associated with increased cancer risk.