Abstract: OBJECTIVE To explore the systemic biological mechanism of Spleen-Stomach Deficiency syndrome (SSD) in the patients with gastric cancer (GC). METHODS 22 GC patients with SSD and 32 healthy volunteers were recruited as controls. The tongue coating microbiota was analyzed by high-throughput sequencing based on 16S rDNA and 18S rDNA genes. Serum cytokines were detected by electrochemiluminescence， and serum metabolomics was analyzed by ultrahigh performance liquid chromatography-mass spectrometer (UPLC-MS). RESULTS Compared with the controls， the GC patients had significantly increased coating Firmicutes and significantly decreased coating Bacteroidetes， Proteobacteria and Fusobacteria（P<0.05）.Linear discriminant analysis (LDA) presented that four coating bacterial genera (Bacillus， Enterococcus， Lactococcus and Serratia) enriched in GC patients. Compared with the controls， the serum levels of GM-CSF， IL-17α， IL-12/IL23P40 and IL-6 were significantly increased in GC patients (P<0.05)， the serum levels of IL-5， TNF-β and IL-4 were significantly decreased (P<0.05)， and nine serum metabolic molecules were significantly increased (P<0.05)， including L-lysine， eicosapentaenoic acid， L-asparagine， lysophosphatidylethanolamine， phosphatidic acid， linoleate， 9-hexadecanoic acid， α-linoleate， and L-phenylalanine. Spearman correlation analysis showed that IL-6， TNF-β and IL-5 were significantly correlated with coating Porphyromonas and Neisseria (P<0.05)， and Neisseria and Fusobacterium were negatively correlated with 9 serum metabolic molecules (P<0.05). CONCLUSION The GC patients with SSD syndrome has altered tongue coating microbiota， which is linking with the different serum cytokines and metabolome. The data provides potential breakthrough point for clarifying the system biological mechanism of SSD syndrome.