Graphene nano-crystalline carbon film/SiO2/p-Si heterostructures were fabricated with SiO2 interlayer thicknesses varying from 0 to 1000 nm, and their in-plane magnetoresistance (MR) was investigated. The results showed that, compared to the 0 nm SiO2 case, the presence of a 5 nm SiO2 interlayer significantly improved the room temperature MR by more than eight times (from 2.5% to 20.9% at 280 K). For SiO2 layers with thicknesses of 50 nm and above, only small negative MR values were observed. For all SiO2 thicknesses, the variations in the mobility of heterostructures were highly consistent with their MR performance. The results of this study provide a practical route to building graphene-based high-performance MR devices suitable for mass production as magnetic sensors and magnetic logic devices.