Vessel embolization is recommended as the first line treatment for unresectable hepatocellular carcinoma (HCC). However, owing to the imprecise vessel embolization and heterogeneous response performance among patients, its survival benefits are often compromised. Herein, we reported an innovative strategy to extensively embolize the tumor by triggering the coagulation cascade, and predict the embolization effect with vessel density assessment. We synthesized manganese dioxide (MnO)/verteporfin (BPD) nanocomposites, in which BPD bound to the tumor vessel endothelial cells (TVECs) and MnO nanosheets served as the carrier. MnO was reduced to Mn ions and self-assembled with BPD to produce nanoBPD, resulting in enhanced TVECs apoptosis and coagulation cascade compared to that with free BPD. Furthermore, multimodal imaging was used to visualize tumor vessel density, which can be used as a predictor to identify the patients who would benefit from embolization. Our findings describe a promising strategy for both tumor eradication and effect prediction to improve survival benefits in unresectable HCC patients.