Abstract: OBJECTIVE To analyze the influencing factors of central nervous system infection (CNSI) and expression of nuclear factor-κB (NF-κB) gene in patients with massive cerebral infarction. METHODS A total of 106 patients with massive cerebral infarction confirmed in Qingdao Hospital of Traditional Chinese Medicine (Haici Hospital) between Jul. 2018 and Jul. 2021 were retrospectively analyzed and were divided into CNSI group (n=31) and non-infection group (n=75) according to presence or absence of CNSI. The levels of interleukin 6 (IL-6), tumor necrosis factor-β (TNF-β), cholinesterase (ChE), immunoglobulins (IgA, IgM, IgG), C-reactive protein (CRP) and procalcitonin (PCT) in cerebrospinal fluid were detected. The expression of NF-κB was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blot. RESULTS The main pathogens of CNSI were coagulase-negative Staphylococcus, Staphylococcus epidermidis and Streptococcus pneumoniae. The levels of IL-6, IgAcsf, IgMcsf, IgGcsf, ChE, CRP and PCT in cerebrospinal fluid in infection group were higher than those in non-infection group (P<0.05). Logistic regression analysis showed that age, combined underlying diseases and increased intracranial pressure were the influencing factors of CNSI in patients with massive cerebral infarction (P<0.05). The levels of NF-κB mRNA and IKKβ mRNA in CNSI group were higher than those in non-infection group, and expression levels of NF-κB, IKKβ and p-IκB proteins were higher than those in non-infection group (P<0.05). CONCLUSION The expression of NF-κB gene was up-regulated and a large number of inflammatory factors were released in patients with massive cerebral infarction and CNSI, leading to continuous progression of the disease, which could be slowed down clinically by controlling the factors affecting the occurrence of CNSI.