Background: Since EGFR inhibitors show a limited therapeutic effect on Glioblastoma multiforme patients, the EGFR/MAPK/STAT5/FN14 signaling pathway becomes vulnerable to the invasive GBM cell population and may be a suitable target for the treatment of GBM. Nanocurcumin consumption and exercise training are probably effective interventions in this signaling pathway. Objectives: This study aimed to investigate the simultaneous effects of exercises training and Nanocurcumin consumption on the EGFR/MAPK/STAT5/FN14/FN14 pathway in the tumor tissue of GBM model rats. Methods: In this study, 40 male Wistar rats were randomly assigned to five groups: 1- control (CON), 2- glioblastoma multiform (GBM), 3- glioblastoma multiform+concurrent training (GBM+CT), 4- glioblastoma multiform+nanocurcumin (GBM+NC), and 5- glioblastoma multiform+nanocurcumin+concurrent training (GBM+NC+CT) groups. The target groups performed aerobic training (20 - 35 minutes at 18 m/min) along with resistance training (climbing the ladder in three sets repeated four times) and received Nanocurcumin at the rate of 100 mg.kg-1.day-1 for four weeks. Gene expression was measured by real-time PCR. Two-way analysis of variance was used for analyzing data. Results: According to our study results, concurrent training significantly reduced the expressions of EGFR, MAPK, STAT5, and Fn14, mRNA compared with GBM group (P < 0.05). Furthermore, nanocurcumin significantly reduced the expressions of EGFR, MAPK, as well as Fn14, mRNA compared with GBM group (P < 0.05). Nanocurcumin+Concurrent training decreased the expressions of EGFR, MAPK, STAT5 as well as Fn14, and mRNA compared with the GBM group (P < 0.05). A significant reduction was recorded for all mRNA expression levels in the GBM+NC+CT group compared with those in the GBM+NC group (P < 0.05). Conclusions: In sum, combined exercises and nano curcumin consumption may have been adopted as a non-pharmacological strategy to modulate the expression of EGFR/MAPK/STA
