Objective To investigate the relationship of interleukin (IL)-lβ and IL-6 levels with the severity of traumatic brain injury (TBI) and their clinical significance.Methods A total of 780 patients with TBI, who were admitted to our hospital from April 2009 to April 2013, were divided into mild, moderate, severe, and highly severe groups. The levels of IL-lβ and IL-6 in serum and cerebrospinal fluid (CSF) were measured. The IL-lβ and IL-6 levels were compared between these groups, and their clinical significance was analyzed.Results IL-lβ and IL-6 levels were significantly increased in the mild, moderate, severe, and highly severe groups. The severe and highly severe groups had significantly higher IL-lβ and IL-6 levels than the other two groups, while the patients who died had higher IL-lβ and IL-6 levels than other patients.Conclusions The levels of IL-lβ and IL-6 in serum and CSF are closely related to the severity of TBI and can be used as clinical monitoring indices.