This study aimed to observe whether liposomal quercetin (LQ) can enhance the effect of microwave ablation (MWA) on hepatic parenchyma destruction. Forty-eight rabbits were randomly divided into three groups: LQ group, MWA group and LQ + MWA group. Serum and liver samples were collected. The coagulation volume (CV) of hepatic parenchyma, histopathological changes and liver function were compared. Hepatocyte apoptosis was examined through TUNEL. The expression of heat shock protein 70 (HSP70), hypoxia-inducible factor-1α (HIF-1α) and tumor necrosis factor-α (TNF-α) were analyzed. Compared with MWA group, the CV of coagulation necrosis in liver was significantly increased in LQ + MWA group. TUNEL results showed that the hepaocyte apoptosis was higher in LQ + MWA group than MWA group on 12 h, 24 h and 3 d, respectively. HSP70 and HIF-1α expression in both MWA group and LQ + MWA group were increased at 12 and 24 hours, peaked on day3 and dropped on day7. Compared with MWA group, HSP70 and HIF-1α expression were lower in LQ + MWA group. On the contrary, TNF-α expression was decreased in MWA group and LQ + MWA group compared with LQ group. In conclusion, LQ increased hepatocyte apoptosis and MWA-induced hepatic parenchyma destruction through suppressing HSP70 and HIF-1α expression in liver surrounding ablation zone and increasing TNF-α expression.