Despite chemotherapy has been widely used for tumor therapy, the serious side effect is still a major challenge. Recently, two dimensional nanomaterial-based drug delivery systems have attracted wide concern due to their high drug loading and low side effect. In addition, some kinds of nanomaterials can directly act as a photosensitizer to induce cancer destruction. In this study, we developed a drug delivery system of mixture of high/low molecular weight branched polyethylenimine-polyethylene glycol-reduced graphene oxide (mBPEI-PEG-rGO) using reduced graphene oxide as matrix. A model drug of doxorubicin (DOX) was loaded on the nanocomposites with the efficiency of 81% and the release rate of more than 50% at acidic environment. In vitro experiments indicated that mBPEI-PEG-rGO-DOX with enhanced stability and biocompatibility efficiently delivered and released DOX into cells mainly through micropinocytosis and killed SMMC-7721 cells by inducing reactive oxygen species (ROS) and cell apoptosis. Furthermore, in vivo experiments indicated that the combination of intratumoral injection of mBPEI-PEG-rGO-DOX and local laser irradiation nearly ablated hepatocarcinoma. In conclusion, this new drug delivery system provided an alternative for combinational photothermal and chemotherapy against hepatocarcinoma.