The growing demand of PVC calls for a more sustainable 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 poses severe threads to human health and the environments. This stimulates numerous researches in the past decades on hunting alternative candidates to replace the mercury catalysts. Among the large numbers of catalyst fami-lies, distinct single-atom metal catalysts have been predicted or demonstrated as promising catalytic systems in the hydrochlorina-tion chemistry, thus stimulating a new wave in the broader explorations of this distinctive catalyst groups in the last five years. In this Review, we summarize the recent advances of single-atom catalysts in acetylene hydrochlorination with the focus on their syn-thesis 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 strategy, recognition of performance descriptors, and developments of on-site characterization techniques are provided.