In this study, we showed that GPR41 and GPR43 are moderately expressed in human HCC, and we found that a SCFA, propionate, enhanced the chemosensitivity of HepG2 cells to cisplatin by inducing TNF-α expression via GPR41 activation involving Gi/o and particularly Gβ/γ. Here, FFAR3 is linked to hepatocellular carcinoma.