Multifunctional nanocomposites that possess imaging and high-performance therapeutic features are experiencing a surge in interest in the precision clinical anticancer treatment. In this work, we reported the fabrication and bio-application of a novel persistent luminescence-polypyrrole nanocomposite (LPLNP@SPP) for photoacoustic/persistent luminescence (PA/PL) dual-modal imaging guided photothermal therapy (PTT). The construction of LPLNP@SPP avoids the PL quenching of LPLNP-OH by the polypyrrole-coating, and thus enables the combination of PL and PTT. The LPLNP@SPP shows excellent biocompatibility, long lasting near-infrared (NIR) PL emitting without in situ excitation and high-contrast PA signals. Meanwhile, this nanocomposite exhibits strong NIR absorbance and exceptional photothermal conversion capability, which provides notable potential for imaging-guided antitumor therapy. Thus, our work highlights the dual-functional core-shell LPLNP@SPP as a feasible theranostic nanoplatform for cancer diagnosis and therapy.