To investigate the potential molecular mechanism of miR-34a in Sjo<spacing diaeresis>gren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-KB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-KB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-KB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-KB signaling by targeting IKB alpha, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.