We found that <i>H.</i> <i>pylori</i> induced IL-37 secretion by epithelial cells via activation of host pathogen recognition receptors TLR2, TLR4 and NOD1, in addition to the <i>H.</i> <i>pylori</i>-encoded cag pathogenicity island, revealing that <i>H.</i> <i>pylori</i> utilises multiple mechanisms to induce IL-37 production during infection. Here, TLR4 is linked to infection.