This study investigated the association of tumor necrosis factor-alpha (TNF-alpha)-308, -238, and -863 polymorphisms with osteoarticular tuberculosis (OA-TB) prognosis in a Hebei population. Genomic DNA was extracted from venous blood samples of 120 OA-TB patients and 100 healthy volunteers. TNF-alpha-308, -238, and -863 were analyzed by PCR-restriction fragment length polymorphism; genotype and allele frequencies were calculated. Serum TNF-alpha level was significantly higher in OA-TB patients (283.16 +/- 51.68 ng/L) than in control (122.54 +/- 54.65 ng/L; P < 0.05). Higher frequency of TNF-alpha-308 GG genotype in healthy volunteers (91.0%) than in OA-TB patients (79.2%) indicated that it was a protective factor against OA-TB (OR = 0.405, 95% CI = 0.147-0.657, P = 0.007). Higher frequencies of TNF-alpha-308 GA genotype and TNF-alpha-308 allele (A) in OA-TB patients (20.8 and 10.4%, respectively) than in healthy volunteers (8.0 and 5.0%, respectively) indicated an association with increased risk of OA-TB (OR = 3.112, 95% CI = 1.5206.343, P = 0.003; OR = 3.109, 95% CI = 1.676-6.538, P = 0.006; respectively). Haplotype association analysis of TNF-alpha polymorphisms (308/238/863) showed a higher frequency of TNF-alpha AGA in OA-TB patients (12.1%) than in healthy volunteers (3.5%), indicating that it was a risk factor for OA-TB (OR = 4.201, 95% CI = 1.809.91, P = 0.010). TNF-alpha-308 G/A and TNF-alpha AGA (308/238/863) were associated with a predisposition to OA-TB, which could aid clinical detection, prevention, and prognosis of OA-TB.