Accumulating evidences have demonstrated that lipopolysaccharide (LPS) represents the important etiologic factor for sepsis. Some previous studies have reported the relationship between common polymorphisms rs4986790 and rs4986791 in the coding gene for this receptor and the susceptibility to sepsis, but there were distinct divergences between those findings. We therefore designed this meta-analysis incorporated 28 published articles containing 6,537 sepsis patients and 8,832 controls for a more comprehensive conclusion on this matter. Odds ratios (ORs) and 95% confidence interval (95% CIs) were calculated to evaluate the association of toll like receptor 4 gene polymorphisms rs4986790 and rs4986791 with sepsis risk. Heterogeneity between included studies was inspected using Q test, and sensitivity analysis was implemented via sequential deletion of each included study to investigate the stability of overall estimates. Funnel plot and Egger's test were adopted to examine publication bias across selected studies. We found no significant association for either the polymorphism rs4986790 or rs4986791 with sepsis susceptibility in total analysis under any genetic models. Neither did we after combining these two polymorphisms. The results of this meta-analysis suggest that the rs4986790 and rs4986791 polymorphisms in toll like receptor 4 gene may have no statistically significant influence on sepsis susceptibility.