As regulations on greenhouse gas emission have strengthened globally, the demand for improved fuel efficiency in automobiles continues to rise. In response, the tire industry is actively conducting research to improve fuel efficiency by enhancing tire performance. In this study, silica-filled epoxidized natural rubber (ENR)/butadiene rubber (BR) blend compounds were manufactured according to ENR types and silica contents, and their physical properties and vulcanizate structure were evaluated. ENR-50, which has a higher epoxide content than ENR-25, exhibited stronger filler-rubber interaction, resulting in superior abrasion resistance. In addition, because of its high glass transition temperature (Tg), the wet grip performance of ENR-50 improved, even though the rolling resistance increased. Increasing the amount of silica had little effect on the abrasion resistance due to the increase in filler-rubber interaction and decrease in toughness. In addition, ENR-50 exhibited better wet grip performance; however, the rolling resistance increased. The results indicated that truck bus radial (TBR) tire tread compounds can be designed by applying ENR-50 to improve wear resistance and wet grip performance. In addition, by applying ENR-25 and reducing the silica contents improve fuel efficiency.