The growing demand for polyvinyl chloride (PVC) calls for a cleaner technology for its production. Nonetheless, acetylene hydrochlorination, an industrially relevant technology for the manufacture of vinyl chloride monomer of PVC, is hampered by the use of toxic and volatile mercury chloride catalysts that pose severe threads to human health and the environments. This stimulated numerous research studies in the past decades on hunting alternative candidates to replace the mercury catalysts. Among the large numbers of catalyst families, distinct single-atom metal catalysts have been predicted or demonstrated as promising catalytic systems in the hydrochlorination chemistry, thus stimulating a wave in the broader explorations of this distinctive catalyst group in the last five years. In this Review, we summarize the recent advances of singleatom catalysts in acetylene hydrochlorination with the focus on their synthesis methods, catalytic performance, and reaction mechanism. The catalyst categories include single metal atoms of Au, Pt, Pd, Ru, Cu, and Fe and diatomic systems. Perspectives on the challenges and directions for future development regarding the innovation of synthetic strategies, recognition of performance descriptors, and developments of on-site characterization techniques are provided.