Here, we report the synthesis of reduced graphene oxide@mesoporous silica (denoted as rGO@mSiO2) sandwich-like sheets by an oil–water biphase stratification approach. The resultant rGO@mSiO2 nanosheets possess a uniform sandwich-like structure, ultrathin thickness (∼50 nm), large aspect ratio, high surface area (∼755 m2/g), and enlarged and tunable pore size (from 2.8 to 8.9 nm). Significantly, the mesochannels are oriented perpendicularly to graphene surfaces and shaped like a funnel, which facilitates drug loading and releasing. The influences of the concentration of precursor, solvent, GO sheet, and reaction temperature on the formation of the sandwich-like rGO@mSiO2 nanosheets have been systematically investigated. The resultant nanosheets with a pore size of ∼8.9 nm show the maximum loading capacity of bovine β-lactoglobulin (55.1 wt %). The protein releasing process in the simulated body fluid suggests that the release can be controlled from 20 to 60 h simply by adjusting the pore size. In addition, the degradability of rGO@mSiO2 nanosheets can be well-controlled by tuning the pore size as well. Most importantly, the nanosheets exhibit a rapid photothermal heating under the near infrared (NIR) irradiation. Therefore, the resultant nanosheets would have a hopeful prospect in a large–molecule–weight drug delivery system, which have both the chemical and photothermal therapeutic functions.