Owing to better stability and biosafety, heterogeneous Cu nanoparticles (CuNPs) have been put forward as a promising candidate to complete the Cu­(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. However, the inherent poor activity of Cu(0) deterred its wide bioapplication. Herein, we employed near-infrared (NIR) light to dual-promote the CuAAC reaction of a biocompatible heterogeneous copper nanocatalyst through photodynamic and photothermal effects in vitro and in vivo. Specifically, the photodynamic activity could promote the conversion of Cu(0) to Cu­(I) to accelerate the catalytic process of CuAAC. The high photothermal conversion efficiency (η = 50.6%) could increase the local temperature, further promoting the whole reaction. Then, a drastically increased reaction rate in a living system ranging from cells to nematodes was achieved in our system. Meanwhile, the better antitumor efficacy has determined with in vivo tumor therapy experiments.