Objective To analyze the clinical characteristics and therapy of Listeria monocytogenes (L. monocytogenes) infection. Methods Clinical data of patients with L. monocytogenes infection in a hospital from January 2016 to December 2018 were collected retrospectively, clinical characteristics, laboratory test, antimicrobial use program and prognosis of patients were analyzed. Results A total of 15 patients with L. monocytogenes infection were collected, most of the non-pregnant adults were over 65 years old and with underlying diseases; 14 patients were with septicemia (including 1 case combined with suppurative meningitis), and 1 case with suppurative meningitis. All the adult patients with septicemia had fever, and only 1 neonate had fever; 2 patients with suppurative meningitis had headache, vomiting and other neurological symptoms besides fever. The levels of leukocyte, C-reactive protein and procalcitonin increased in most of the 15 patients, cerebrospinal fluid examination of 2 patients with suppurative meningitis was obviously abnormal. 14 patients improved after receiving penicillin or meropenem therapy alone, or combined use of two drugs, 1 patient was worsened. Conclusion L. monocytogenes mainly causes bloodstream infection or suppurative meningitis in neonates, pregnant women, the elderly, and immunocompromised person, penicillin, ampicillin, meropenem and compound sulfamethoxazole can be used for empirical therapy for L. monocytogenes infection.