The chemical identity of anchoring groups has a great impact on the charge transport in single-molecule junctions. In this paper, a new πconjugated anchoring group, thiazole, with a built-in quantum interference (QI) feature for Au−molecule−Au junction is reported. The charge transport properties of thiazole-end-capped conjugated molecules are investigated by the scanning tunneling microscopy break junction (STMBJ) technique. Experimental results show that the conductance of junctions changes distinctly with the substitution positions of thiazole, which is ascribed to the quantum interference and the change of coupling strength between molecule and electrodes. Notably, the conductance change reaches 331 times, much higher than that of benchmark anchoring group pyridine-terminated molecules. X-ray photoelectron spectroscopy (XPS) experiments and DFT calculations confirm that Au−N and Au−π interactions co-serve as anchoring sources, and the coupling strength between thiazole anchor and electrodes is tunable. These results highlight the built-in QI feature of thiazole anchor and enrich the self-decoupling strategies for conjugated molecules.