Background: The risk of local recurrence of high intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. Combination of HIFU with traditional chemotherapy still remains the unsatisfactory outcome because of off-site drug uptake.Results: Herein, we proposed the strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeting therapy for residual tumor of HIFU ablation. Neutrophils as a carrier, and PEGylated liposome doxorubicin (PLD) as a nanodrug model of chemotherapy, were selected to form an innovative cell therapy drug (PLD@NEs). The targeting performance and therapeutic potential of PLD@NEs were evaluated using hepa1-6 cells and corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation, and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy.Conclusion: This effective integration takes full use of the advantages of both HIFU, chemotherapy and neutrophil, attracting more focus on the practice of improving the existing clinical therapeutics.