Listeria innocua is widely distributed in the environment and food and is considered a non-pathogenic bacterium for both humans and animals. To our knowledge, only a few cases of L. innocua infection in humans and ruminants have been reported. Moreover, there has been no report on human L. innocua meningoencephalitis. Here, we report a case of severe refractory meningoencephalitis in a three-year-old boy after infection with L. innocua. The child's first symptoms were a runny nose, high fever, and rashes, which quickly progressed to unconsciousness and convulsions. The initial analysis of cerebral spinal fluid revealed remarkably elevated protein levels and increased white blood cells count. The blood culture of the patient in the early stage was positive for L. innocua. In addition, his brain imaging tests were observed dynamically, and the result showed a speedy progression from multiple intracranial abnormal signals to hydrocephalus and interstitial cerebral edema. After receiving antibiotics and symptomatic treatment for nearly 3 months, the patient's condition improved markedly. However, he still had residual complications such as hydrocephalus. Although L. innocua is considered harmless, it can still cause disease in humans, even severe meningoencephalitis, with rapid progression and poor prognosis. Early discovery, diagnosis, and treatment are necessary to elevate the survival rate and life quality of those patients. Antibiotics should be used with sufficient duration and dosage. Cephalosporins are not suitable for the treatment of L. innocua meningoencephalitis and penicillin antibiotics are preferred for children. The presentation of this case will help to expand our knowledge of Listeria infections and provide a potential candidate for pathogens causing severe childhood central nervous system infection.