Machine learning was used for idenfifying possible pathogenesis-related long non-coding RNAs (lncRNAs) in labial gland tissue and whole blood of Sjogrens syndrome (SS) patients, and investigating the correlation between the lncRNA with immune cell infiltration in labial gland tissue. The expression data of SS labial gland tissue and whole blood were obtained from the GEO database, and the data were normalized and processed for differential analysis to obtain lncRNA expression profiles. Common lncRNAs were screened and intersected by two machine learning methods. Based on CIBER-SORT software, 22 immune cell infiltration situations in labial gland tissues were calculated,and the correlation between key lncRNAs and immune cell infiltration was analyzed. The correlation between key lncRNAs and clinical traits in whole blood was analyzed and ROC curves were plotted. Key lncRNA co-expression encoding protein genes were analyzed and KEGG signaling pathway analysis was performed. One SS key lncRNA (HCP5) was identified, and HCP5 was upregulated in labial gland tissue and whole blood. Immuno-infiltration analysis showed that the proportion of γδ T cells, macrophages, and CD4+ memory T cells increased in SS labial gland tissue, while the proportion of plasma cells decreased in SS labial gland tissue. The expression of HCP5 was positively correlated with the infiltration of γ/δ T cells and CD4+ memory T cells. In whole blood, HCP5 significantly correlated with ANA, IgG, anti-SSA antibodies, anti-SSB antibodies, and ESSDAI. The ROC diagnostic curve results in different datasets showed that the AUCs of HCP5 were 0.833 and 0.877. KEGG analysis showed that the function of proteins co-expressed with HCP5 in the labial gland was focused on signaling pathways such as antigen processing and presentation and B cell receptor signaling pathway, while the proteins co-expressed with HCP5 in whole blood functioned in signaling pathways such as metabolic pathways and apoptosis. HCP5 may affect the pathogenesis and progression of the disease by regulating the infiltration of immune cells in the labial gland tissue, and may be a potential diagnostic and therapeutic target for SS. [ABSTRACT FROM AUTHOR]