The present study, with all potential limitations derived from an ‘‘in vitro’’ investigation, points out for the first time that polydatin reduces iROS production and lipid peroxidation as well as the expression of pro-inflammatory chemokines through MyD88 and NLRP3 mediated pathways; based on the results obtained, further in vivo studies in renal cancer-bearing mice treated with sunitinib are suggested. Here, MYD88 is linked to renal carcinoma.