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In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)- modified and oxidized sodium alginate (OSA) -functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)- irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for Pgp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity (Scheme 1).