It is well known that the human innate immune and adaptive immune response play important role in tuberculosis (TB) infection and progress. Emerging evidence shows that FOXO3 plays an important role in the human immune system. Recent research has shown that the FOXO3 genetic variants are associated malaria infection. In this study, 268 confirmed TB patients, 321 patients with latent tuberculosis infection (LTBI), and 475 TB-free controls were recruited; the single-nucleotide polymorphism (SNP) rs12212067: T > G in FOXO3 was genotyped using predesigned TaqManA (R) allelic discrimination assays. The results showed that the G allele of rs12212067 in FOXO3 was more common in health control and the latent TB group compared with the active TB group (p = 0.048, odds ratio (OR) 95 % confidence intervals (CI) = 1.37 (1.00-1.89); p = 0.042, OR 95 % CI = 1.42 (1.01-1.99), respectively); furthermore, within active TB patients, the G allele of rs12212067 in FOXO3 was more frequent in extra-pulmonary tuberculosis (EPTB) group compared to pulmonary tuberculosis (PTB) group (p = 0.035, OR 95 % CI = 0.57 (0.33-0.97). In conclusion, this study found that rs12212067 in FOXO3 was associated with increased risk of active TB. The minor G allele might be a protection factor which was found more common in latent TB patients and healthy controls than active TB patients.