Our previous studies have confirmed that transforming growth factor-β (TGF-β) plays an important role in tumor metastasis, and the serum deprivation protein response (SDPR) is a potential downstream target of TGF-β. However, the role and mechanism of SDPR in gastric cancer are still unclear. We performed gene microarray, bioinformation analysis, combined within vivoandin vitroexperimental verification, we identified that SDPR is significantly downregulated in gastric cancer, and participates in TGF-β-mediated tumour metastasis. Mechanically, SDPR interacts with extracellular signal-regulated kinase (ERK) and inhibits fatty acid metabolism key gene Carnitine palmitoyl transferase 1A (CPT1A) at transcriptional level by supressing ERK/PPAR pathway. Our findings suggest that the TGF-β/SDPR/CPT1A axis play an important role in the fatty acid oxidation of gastric cancer, and provides a new insight into the crosstalk of tumour microenvironments and metabolism reprogramming and suggest that strategies to intervene the fatty acid metabolism may therapy gastric cancer metastasis.