Reduced graphene oxides (RGO)-based materials exhibit high carrier mobility and selective recognition ability to NO2, making them constitute promising platform for room-temperature NO2 detection. However, the low sensitivity becomes the main bottleneck for their further development. Here, we demonstrate that synergy of Pd nanoparticles (NPs) and oxygen vacancies can modulate the surface active sites over SnO2 NPs modified RGO hybrids (labeled as SR), leading to improving the sensitivity of room-temperature NO2 sensors. Experimentally, a wet-chemical method was used to introduce oxygen vacancies onto SR, leading to forming SR with rich oxygen vacancies (labeled as SR-Vo), which were subsequently deposited with Pd NPs, resulting in preparing Pd NPs loaded SR-Vo hybrids (labeled as Pd-SR-Vo). Impressively, the response value to 1 ppm NO2 of Pd-SR-Vo hybrids reaches to 9.8, which is much higher than that of R-Vo hybrids (5.6) and SR hybrids (3.3). The improvement of sensitivity toward NO2 for Pd-SR-Vo hybrids is attributed to the synergy effect of Pd NPs and oxygen vacancies, including shortening the band gap of Pd-SR-Vo hybrids with raising conduction band level, widening the width of electron depletion layer between SnO2-Vo and RGO, introducing Schottky contact between Pd and SnO2-Vo, improving efficiency for gas sensing reaction. This work not only provides an efficient approach to fabricate high-performance NO2 sensors, but also opens a new avenue for sensing materials design and modification.