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We aim to identify the common genes, biological pathways and treatment targets for primary Sjögren's syndrome patients with varying degrees of fatigue features. We select datasets about transcriptomic analyses of Primary Sjögren's syndrome(pSS) patients with different degrees of fatigue features and normal controls in peripheral blood. We identify common differentially expressed genes(DEGs) to find shared pathways and treatment targets for pSS patients with fatigue and design protein-protein interactions (PPIs) network by some practical bioinformatics tools. And hub genes are detected based on the PPIs network. We perform biological pathways analysis of common genes by gene ontology(GO) terms and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway. Lastly, potential treatment targets for pSS patients with fatigue are found by the Enrichr platform. We discovered 27 DEGs are identified in pSS patients with fatigue features and the severe fatigued pSS-specific gene being RTP4. DEGs are mainly localized in the mitochondria, endosomes, endoplasmic reticulum, cytoplasm and are involved in the biological process by which interferon acts on cells and cells defend themselves against viruses. Molecular functions mainly involve the process of RNA synthesis. The DEGs of pSS are involved in the signaling pathways of viruses such as hepatitis C, influenza A, measles, and EBV. Acetohexamide PC3 UP, suloctidil HL60 UP, prenylamine HL60 UP, chlorophyllin CTD 00000324 are the four most polygenic drug molecules. PSS patients with fatigue features have specific gene regulation and chlorophyllin may alleviate fatigue symptoms in pSS patients.