Docetaxel (Doc) has extraordinary activities against a variety of solid tumors. However, the clinical efficacy of Doc is limited due to its poor solubility, low selective distribution, fast eliminationin vivo, etc. In the present study, Doc was incorporated into the core-shell structure of nanoparticles prepared based on our previous work. The obtained docetaxel-loaded nanoparticles (DOCNP) were characterized with various biophysical methodologies, and its antitumor efficacy against malignant melanoma was evaluated bothin vitroandin vivo. Our results indicated that Doc could be incorporated into the nanoparticles with high encapsulation efficiency (>90%). The incorporated Doc can be released from DOCNP in a sustained manner.In vitrocytotoxicity studies indicated that DOCNP could effectively kill B16 cells and show a dose- and time-dependent efficacy. Furthermore, intratumoral administration revealed that DOCNP has significantly higher antitumor effect and lower toxicity to normal cells and tissues than free Doc. These results suggest that DOCNP may be a promising drug delivery system in therapy for malignant melanoma.