Objective To investigate the expression and clinical significance of Small Nucleolar RNA Host Gene 22 (SNHG22) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), and its effects on the proliferation and cytokine secretion of Raji cells. Methods Peripheral blood samples were collected from 78 SLE patients and 78 healthy controls. Mononuclear cells were isolated, and SNHG22 expression levels were measured. The predictive value of SNHG22 for SLE diagnosis was evaluated using receiver operating characteristic (ROC) curve analysis. Clinical indicators, including anti-double-stranded DNA (dsDNA) antibodies and 24-hour urinary protein, were collected from SLE patients, and the correlation between these indicators and SNHG22 expression was analyzed. SNHG22 was silenced in Raji cells using siRNA technology, and cell proliferation was assessed by CCK-8 and EDU staining assays. The secretion levels of inflammatory cytokines IL-2, IL-6, IL-10, and TNF-α were measured using ELISA. Results SNHG22 expression in PBMCs was significantly higher in SLE patients compared to controls. ROC curve analysis showed an area under the curve (AUC) of 0.848 for SNHG22 expression, indicating good potential for SLE prediction. SNHG22 expression was significantly higher in PBMCs of SLE patients with positive anti-dsDNA antibodies and urinary protein compared to those who were negative. Silencing SNHG22 significantly reduced its RNA expression in Raji cells (P＜0.001), inhibited cell proliferation (P＜0.001), and decreased the secretion of inflammatory cytokines (P＜0.001). Conclusion SNHG22 is highly expressed in PBMCs of SLE patients. Silencing SNHG22 inhibits Raji cell proliferation and modulates the secretion of inflammatory cytokines, suggesting that SNHG22 may be a potential biomarker for the diagnosis and treatment of SLE