Aim: To clarify the role of polymorphisms rs4986790 and rs4986791 in TLR-4 with susceptibility to neonatal sepsis. Methods: To evaluate the possible correlation of polymorphisms rs4986790 and rs4986791 with sepsis risk, odds ratios (ORs) were calculated. The heterogeneity was evaluated by χ2-based Q-test. Results: For rs4986790, ORs were 1.36 (95% CI: 1.05–1.79, p = 0.017) and 1.84 (95% CI: 0.04–7.9, p = 0.410) under AG+GG versus AA and G vs. A models, respectively. For rs4986791, ORs were 2.22 (95% CI: 1.25–3.94, p = 0.006) and 2.20 (95% CI: 1.26–3.85, p = 0.005) under CT+TT versus CC and of T versus C models, respectively. Conclusion: The rs4986790 and rs4986791 polymorphisms in TLR-4 could influence the sepsis susceptibility in neonates.