Background: Genetic susceptibility has been suggested as an important explanation for individual risk for tuberculosis. The association between vitamin D receptor (VDR) FokI gene polymorphisms and the risk of tuberculosis have been studied in several populations; but results were inconsistent. Objectives: This study aimed to determine the influence of vitamin D status and frequency of association of VDR FokI (rs2228570) polymorphism on susceptibility to pulmonary tuberculosis. Methodology: A case-control study was conducted between 40 pulmonary tuberculosis patients and 40 control subjects. Serum vitamin D level and VDR FokI gene (rs2228570) polymorphism were tested. Results: Tuberculosis patients had significant lower vitamin D level compared to controls (P = 0.002). Patients showed significantly higher frequencies of VDR FokI (rs2228750) Ff, ff genotypes and f allele than controls (P = 0.023, 0.014, <0.001 respectively) with significant lower vitamin D level in patients with ff compared to patients with FF or Ff genotypes (P = 0.017). Excess smoking, vitamin D insufficiency and VDR FokI (rs2228750) (Ff+ff) genotypes were found predictors for susceptibility to tuberculosis infection. Conclusion: vitamin D deficiency plays a role as a risk factor for tuberculosis and VDR FokI (rs2228750) polymorphism may be partially responsible for host susceptibility to human tuberculosis in Egyptians.