Abstract Objectives Britanin was explored for the antitumour effect on gastric cancer, which is a sesquiterpene lactone (SL) extracted from Inula japonica. Methods In the present study, cell viability assays were performed to evaluate the antiproliferation effect of Britanin on gastric cancer cells. Tumour development in BGC-823 cell-bearing nude mice was monitored in real-time after Britanin treatment via a bioluminescent imaging method. Western blotting analysis and enzyme-linked immunosorbent assays detected proteins associated with the nuclear factor (NF)-κB signalling pathway. Key findings Britanin can suppress the proliferation of gastric cancer cells in vitro and the growth of tumours in vivo. In the treatment group, decreased levels of p65 and phosphorylated (p)-p65 were observed. This indicated that NF-κB plays an important role in the antitumour effect of Britanin. Furthermore, considering the additional role of NF-κB in the immune system, the levels of the downstream molecules interleukin (IL)-2 and the cytokine IL-10 were subsequently determined in vivo. An increase in the IL-2 level and a decrease in the IL-10 level indicated that Britanin elicited an enhanced immune response. Conclusions Britanin may be a promising candidate for gastric cancer chemotherapy, and its anticancer effect likely depends on an NF-κB-mediated immune response.