Palladium, as a toxic heavy metal, poses a great threat to the environment and human health. Therefore, it is essential to achieve the purpose of detecting trace amounts of palladium. In this paper, a probe CM480 based on the Tsuji–Trost reaction has been developed that can effectively recognize Pd²⁺, resulting in a large fluorescence “turn-on” response. CM480 exhibits excellent properties including rapid response (within 3 minutes), low detection limit (1.65 nM), good linearity (R² = 0.9945) and specific selectivity. Moreover, CM480 shows superior recovery that it has great potential for being applied in real samples.