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Genetic variants in <i>FOXO3</i> are associated with longevity. Here, we assessed whether blood DNA methylation at <i>FOXO3</i> was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (<i>n</i> = 409 cases), colorectal (<i>n</i> = 835), gastric (<i>n</i> = 170), kidney (<i>n</i> = 143), lung (<i>n</i> = 332), prostate (<i>n</i> = 869), and urothelial (<i>n</i> = 428) cancer and B-cell lymphoma (<i>n</i> = 438). Case–control pairs were matched on age, sex, country of birth, and smoking (lung cancer study). Conditional logistic regression was used to assess associations between cancer risk and methylation at 45 CpGs of <i>FOXO3</i> included on the HumanMethylation450 assay. Mixed-effects Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with cancer survival (total <i>n</i> = 2286 deaths). Additionally, using data from 1088 older participants, we assessed associations of <i>FOXO3</i> methylation with overall and cause-specific mortality (<i>n</i> = 354 deaths). Methylation at a CpG in the first exon region of <i>FOXO3</i> (6:108882981) was associated with gastric cancer survival (HR = 2.39, 95% CI: 1.60–3.56, <i>p</i> = 1.9 × 10⁻⁵). Methylation at three CpGs in TSS1500 and gene body was associated with lung cancer survival (<i>p</i> < 6.1 × 10⁻⁵). We found no evidence of associations of <i>FOXO3</i> methylation with cancer risk and mortality. Our findings may contribute to understanding the implication of <i>FOXO3</i> in longevity.