Metal–organic frameworks (MOFs) with tunable structures, high porosity, and abundant active sites are considered to be promising drug delivery systems (DDSs). In this study, novel MOFs-based nanoparticles ([email protected]) were successfully prepared using Zn-based IRMOF-16 as a carrier and curcumin (CUR) as the model drug. This nanocargo delivery platform has dual capabilities, enabling simultaneous drug delivery and fluorescence imaging. In vitro release experiments showed that nanoparticles were released more quickly under mildly acidic conditions, which proved their potential for tumor microenvironment-responsive drug release. Through in vitro cell experiments, it was found that the nano-drug platform had high antitumor cytotoxicity, which may be related to the mechanism of increasing intracellular reactive oxygen species (ROS), reducing intracellular mitochondrial membrane potential (MMP), and inducing apoptosis. In addition, confocal laser microscopy showed that [email protected] could localize to the nucleus to exert an antitumor effect. Meanwhile, [email protected] exhibited superior antitumor activity compared with pure CUR in vitro experiments. The biocompatibility test of IRMOF-16 showed reasonable biosafety, and no evidence of obvious toxicity was observed in vitro. [email protected] has unique advantages with regard to pH response, biocompatibility, and antitumor efficacy, indicating that the nano-drug platform is a promising drug delivery carrier with an antitumor effect.