Aim: To synthesize and evaluate a novel FH peptide-modified ultrasonic nanobubble-loading doxorubicin (FH-NB-DOX) for specially cancer-associated fibroblasts (CAFs) targeting and eradication. Materials & methods: The characteristics, cytotoxicity, contrast-enhanced ultrasound imaging (CEUI), targeting ability and specially eradicating CAFs of these NBs were investigated. Results: FH-NB-DOX (about 208 nm) showed a good CEUI, and achieved higher targeting ability due to the conjunction ability of FH peptide to tenascin C protein high-level expressed in CAFs. Under ultrasound irradiation, FH-NB-DOX could delivery more DOX into CAFs, thus exhibited stronger eradication role compared with NB-DOX and free DOX. Conclusion: These new NBs, which combines the advantages of targeted theranostic agent and CEUI, is expected to be a potential approach for tumor therapy based on CAF targeting.