In search of facile yet efficient therapeutic and imaging nanoagents for cancer treatment, versatile self-reporting gold nanourchins (AuNUs) featuring synergic chemo-photothermal therapies and multimodal imaging are fabricated. AuNUs are synthesized using a surfactant-free approach, and then functionalized with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) and dopamine to form adenosine triphosphate (ATP)-cleavable boronate ester bonds prior to further immobilization with hyaluronic acid (HA) for cancer targeting. Controlled release of an anticancer drug, doxorubicin (DOX), loaded in the interstices of AuNUs, is achieved upon exposure to the overproduced hyaluronidase (HAase) in a tumor microenvironment. The spiny exterior of AuNUs enables their optophysical conversion of near-infrared (NIR) light (808 nm) to heat for photothermal therapy and IR imaging. The surface enhanced Raman scattering (SERS) of AuNUs also allows sensitive and reliable Raman mapping of their cellular uptake in vitro, and intratumoral accumulation in vivo, complementary to conventional photoacoustic imaging (PAI). With a demonstrated ability to eradicate tumors and enable multimodal imaging, AuNUs exemplify ongoing efforts in design and utility of multifunctional nanoplatforms.