Abstract: OBJECTIVE To analyze the risk factors of ventilator-associated pneumonia in patients with mechanical ventilation in the intensive care unit (ICU) and the gene changes of WNT1-induced signaling pathway protein 1 (WISP1)/Toll-like receptor 4 (TLR4)/integrin β5 pathway. METHODS A total of 188 patients with mechanical ventilation in ICU admitted to Shandong Maternal and Child Health Hospital and Shandong Shanxian Central Hospital from May 2018 to Dec 2022 were retrospectively collected in the study, which were divided into the ventilator-associated pneumonia group (n=49) and the non-ventilator-associated pneumonia group (n=139) according to whether the ventilator-associated pneumonia occurred. The pathogenic bacteria distribution of ventilator-associated pneumonia in patients with mechanical ventilation in ICU was analyzed, and gene expression of WISP1/TLR4/ integrin β5 pathway were compared between the two groups. Clinical data of patients were collected, and the risk factors for ventilator-associated pneumonia in patients with mechanical ventilation in ICU were analyzed by univariate and multivariate analysis. RESULTS Ventilator-associated pneumonia occurred in 49 of 188 patients with mechanical ventilation in ICU, with the incidence rate was 26.06%. A total of 58 strains of pathogenic bacteria were isolated, among which 46 strains were gram-negative bacteria, accounting for 79.31%. The expression levels of WISP1 messenger ribonucleic acid (mRNA), TLR4 mRNA and integrin β5 mRNA in the ventilator-associated pneumonia group were higher than those in the non-ventilator-associated pneumonia group (P＜0.05). Multivariate logistic analysis showed that mechanical ventilation duration ≥20 d, increased expression levels of WISP1 mRNA, TLR4 mRNA and integrin β5 mRNA were risk factors for ventilator-associated pneumonia in patients with mechanical ventilation in ICU (P＜0.05). CONCLUSION The main pathogens of ventilator-associated pneumonia in ICU patients with mechanical ventilation were gram-negative bacteria. WISP1/TLR4/ integrin β5 pathway genes might be involved in the occurrence of ventilator-associated pneumonia, and many factors were closely related to the occurrence of ventilator-associated pneumonia in patients with mechanical ventilation in ICU.