This investigation reveals that silencing HSP70 in conjunction with oncolytic vaccinia virus (oncoVV−shHSP70) results in enhanced efficacy against ovarian cancer through the synergistic activation of the intrinsic apoptotic pathway, increasing autophagic flux and ROS generation, and establishing a ROS−autophagy feedback loop that regulates viral replication and pro−inflammatory cytokine expression (Figure 6). Here, HSPA1A is linked to ovarian cancer.