A number of studies have demonstrated that resveratrol (RES) has a variety of biological functions, including cardiovascular protective effects, treatment of mutations, and anti‑inflammatory, anti‑tumor and antiviral effects. In the present study, RES‑loaded nanoparticles (RES‑NPs) were used to protect rhabdosarcoma (RD) cells from enterovirus 71 (EV71) infection, and the relevant mechanisms were also explored. An amphiphilic copolymer, monomethoxy poly (ethylene glycol)‑b‑poly (D,L‑lactide), was used as vehicle material, and RES‑NPs with necessitated drug‑loading content and suitable sizes were prepared under optimized conditions. RES‑NPs exhibited the ability to inhibit the increase of intracellular oxidative stress. The prospective mechanism for the function of RES‑NPs suggested was that RES‑NPs may inhibit the oxidative stress‑mediated PERK/eIF2α/ATF4 signaling pathway, downregulate the autophagy pathway and resist EV71‑induced RD cells injury. Furthermore, RES‑NPs treatment markedly inhibited the secretion of inflammatory factors, including interleukin (IL)‑6, IL‑8 and tumor necrosis factor‑α elicited by EV71 infection. Concomitantly, inhibitors of oxidative stress, endoplasmic reticulum stress (ERS) or autophagy were demonstrated to negate the anti‑inflammatory and antiviral effects of RES‑NPs on EV71‑infected RD cells. These results demonstrated that RES‑NPs attenuated EV71‑induced viral replication and inflammatory effects by inhibiting the oxidative stress‑mediated ERS/autophagy signaling pathway. In view of their safety and efficiency, these RES‑NPs have potential applications in protecting RD cells from EV71 injury.