Abstract: A Hg²⁺ photothermal sensing comprehensive innovative teaching experiment based on temperature signals was designed using problem-based learning (PBL). In this teaching experiment, the CuS nanoparticles (CuS NPs) with high photothermal conversion efficiency were firstly prepared by mechanochemistry-based wet grinding. Then, a novel Hg²⁺ photothermal sensing method was established based on the photothermal signal changes induced by the precipitation displacement reaction between CuS NPs and Hg²⁺. By integrating the research achievements of “Hg²⁺ photothermal sensing” into the experimental teaching process, the innovative teaching design concept of undergraduate chemistry experiments is explored, achieving the guidance of scientific research thinking in designing innovative university chemistry experiments, which is helpful to systematically and comprehensively train students’ ability to discover and solve problems, as well as effectively improve students’ comprehensive utilization of basic knowledge and practical innovation ability simultaneously, so as to promote the reform of undergraduate experimental teaching.