Background: We investigated the effect of a small molecular inhibitor of heat shock protein(HSP), quercetin, on tumor radiofrequency(RF) ablation, and explored the underlying molecular mechanisms.Methods: In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms(control, quercetin alone, RF alone, and combination) for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat shock protein 70(HSP70), cleaved caspase-3 and heat shock factor 1(HSF1) were analyzed after different treatments. In in vitro study, we used quercetin to promote SKHEP-1(hepatic) and MCF-7(breast) cancer cell apoptosis in heat shock cell model, and si RNA was used to block c-Jun and to explore the role of activating protein-1(AP-1) signaling pathways.Results: We found the effects of quercetin plus RFA resulted in increase on the tumor destruction/endpoint survival(26.5±3.4 d) in vivo, compared with RF alone(17.6±2.5 d) and quercetin alone(15.7±3.1 d). Most importantly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. Furthermore, quercetin directly down-regulated expression of HSF1 in vitro, which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using si RNA mediated targeting of c-Jun.Conclusions: These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors. Background: We investigated the effect of a small molecular inhibitor of heat shock protein (HSP), quercetin, on tumor radiofrequency (RF) ablation, and explored the underlying molecular mechanisms. Methods: In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms (control, quercetin alone, RF alone, and combination) for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat In vitro study, we used quercetin to promote SKHEP-1 (hepatic) and MCF-7 (breast) cancer cell (HSP70), cleaved caspase-3 and heat shock factor 1 apoptosis in heat shock cell model, and si RNA was used to block c-Jun and to explore the role of activating protein-1 (AP-1) signaling pathways. Results: We found the effects of quercetin plus RFA resulted in increase on the tumor destruction / e ndpoint survival (26.5 ± 3.4 d) in vivo, compared with RF alone (17.6 ± 2.5 d) and quercetin alone (15.7 ± 3.1 d). Mostly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. , which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using si RNA mediated targeting of c-Jun. Conclusions: These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors.