Objective: The study aimed to explore the expression of microRNA-146a (miRNA-146a) in the peripheral blood of patients with Alzheimer's disease (AD) and its correlation with disease severity. Methods: We recruited 122 AD patients (AD group) who were further divided into mild, moderate, and severe subgroups according to the Mini-Mental State Examination (MMSE) score and 122 healthy people (control group) during the period of January 2017 to January 2019. The levels of miRNA-146a from peripheral blood, Toll-like receptor 4 (TLR4) on peripheral blood monocytes, and C-reactive protein (CRP) and procalcitonin (PCT) in serum were compared between the groups and among the subgroups. The correlations among miRNA-146a, TLR4, CRP, and PCT levels and MMSE scores were analyzed among the three subgroups. Moreover, receiver operating characteristic curve analysis was used to assess the diagnostic value of the above indicators in AD. Results: Compared with the control group, miRNA-146a, TLR4, CRP and PCT levels increased significantly in the AD group (P<0.05), and also rose markedly as the disease progressed (P<0.05). According to the correlation analysis, significant negative correlations existed between miRNA146a, TLR4, CRP and PCT levels and MMSE scores (P<0.05), while a positive correlation existed between levels of miRNA-146a and TLR4 (P<0.05). Furthermore, the receiver operating characteristic curve analysis demonstrated that miRNA-146a and TLR4 are of great clinical value (AUC>0.90), and CRP and PCT are of certain clinical value for screening of AD (AUC>0.70). Conclusion: MiRNA-146a, which may participate in the pathogenesis of AD via TLR signaling pathway, is closely correlated with TLR4. In the diagnosis of AD, miRNA-146a and TLR4 are diagnostically significant.