Objective TNF?α monoclonal antibody drugs are widely used to treat conditions such as rheumatic arthritis and ankylosing spondylitis. On the other hand, it is also a wide concern that the application of these drugs may increase the susceptibility of patients to infections such as tuberculosis and listeriosis. The aim of this study was to establish a mouse model of Listeria monocytogenes infection and to evaluate the effect of TNF?α monoclonal antibody on the host susceptibility to this infection. Methods Six SPF 14?week old female C57BL/6 mice and 12 SPF 14?week old female TNF?α humanized mice were injected with saline or adalimumab intravenously, and challenged with intraperitoneal injection of 10⁴ CFU Listeria monocytogenes 24 h later. After one day or 4 days, the mice were sacrificed to examine the pathological lesions and the bacterial load in the spleen and liver. Results Four days after infection, the area of microabscess in the liver tissues was significantly increased in the adalimumab?treated group. The bacterial load in the spleen and liver tissues of the adalimumab?treated group was significantly higher than that of the C57BL/6 mouse control group and TNF?α humanized mouse control group ( P < 0. 05). However, the distribution of macrophages in the liver tissues and B cells in the spleen tissues were similar among groups. Conclusions TNF?α plays an important role in the host immune responses to Listeria monocytogenes infection. After the intervention with TNF?α monoclonal antibody, the progress of host disease is significantly exacerbated.