Herein, we successfully developed a new multifunctional antibacterial system, which combined mechano-bactericidal (Au-nanostars) and photothermal (MoS2) mechanism. Meanwhile, the targeting molecule of vancomycin was modified on the surface of MoS2-Au nanocomposites (Van-MoS2-Au), that generally yield high efficiency in antibacterial performance due to their effective working radii. Van-MoS2-Au nanocomposites were capable of completely destroying both gram-negative (E. coli) and gram-positive (B. subtilis) bacteria under 808 NIR laser irradiation for 20 min, and nearly no bacterial growth was detected after 12 h incubation. Moreover, these nanocomposites could destruct the refractory biofilm as well, which was a much more difficult medical challenge. The new antibacterial nanomaterials might offer many biomedical applications because of the biocompatibility and strong antibacterial ability.