Interferon (IFN) signatures are upregulated in patients with primary Sjögren’s syndrome (pSS) and IFNs are considered to play a pathogenic role in pSS. As IFN signaling involves Janus kinase (JAK) pathway, we set out to investigate whether a selective JAK1 inhibitor, filgotinib would suppress pathogenic cytokine /chemokine production of primary salivary gland epithelial cells (pSGEPs) in salivary gland organoid co-culture system and ameliorate disease-related parameters in non-obese diabetic (NOD) mice, an animal model SS. Microarray and validation PCR was conducted using RNAs of salivary gland obtained from patients with pSS. Expression of DEGs-IFIT1, IFIT2, IFI44L, ISG15 and RSAD2- and B cell activating factor (BAFF) and interferon gamma-inducible protein (IP10) were increased by the area of lymphocyte foci in the salivary gland from pSS patients. The effect of filgotinib on the expressions of BAFF and IP10 of the pSGEPs obtained from pSS patients was investigated. Filgotinib suppressed pSTAT1Y701, pSTAT3S727 but not PIAS1/SOCS1 or PIAS3/SOCS3 in HSG cell line. And knockdown of interferon-stimulated factors revealed less expression of BAFF and IP10 by IFNα in salivary gland organoid culture. Filgotinib suppressed the differentiation of IL-21 producing T follicular helper (Tfh) cells when peripheral blood mononuclear cells were co-cultured with IFNα-stimulated pSGEPs in salivary gland organoid culture. Finally, Filgotinib (1.5mg/kg) or vehicle was intraperitoneally injected to NOD mice three times per week. Salivary flow rates of filgotinib-treated mice were greater than those of controls. Histologic evaluation of the salivary gland revealed that the lymphocytic infiltration was markedly reduced in the mice treated with filgotinib. Our data suggest that JAK1 inhibition controls pathogenic function of pSGEPs and it may be a novel therapeutic approach for pSS.