Background: Loss of function of the p53 gene is implicated in defective apoptotic responses of tumors tochemotherapy. Although the pro-apoptotic roles of eugenol and capsaicin have been amply reported, theirdependence on p53 for apoptosis induction in gastric cancer cells is not well elucidated. The aim of the study wasto elucidate the role of p53 in the induction of apoptosis by eugenol and capsaicin in a human gastric cancer cellline, AGS. Materials and Methods: AGS cells were incubated with or without various concentrations of capsaicinand eugenol for 12 hrs, in the presence and absence of p53 siRNA. Cell cycling, annexin V and expression ofapoptosis related proteins Bax, Bcl-2 ratio, p21, cyt c-caspase-9 association, caspase-3 and caspase-8 were studied. Results: In the presence of p53, capsaicin was a more potent pro-apoptotic agent than eugenol. However, silencingof p53 significantly abrogated apoptosis induced by capsaicin but not that by eugenol. Western blot analysisof pro-apoptotic markers revealed that as opposed to capsaicin, eugenol could induce caspase-8 and caspase-3even in the absence of p53. Conclusions: Unlike capsaicin, eugenol could induce apoptosis both in presence andabsence of functional p53. Agents which can induce apoptosis irrespective of the cellular p53 status have immensescope for development as potential anticancer agents.