Clostridium perfringens is a gram-positive anaerobic spore-forming bacterium which is widely spread in nature. The bacterial pathogen is able to secret protein toxins and enzymes which contribute to its pathogenicity. The regulation of gene expression of these toxins is controlled by a network that establishes cell-cell communication. In order to produce toxins, bacterial cells communicate through producing and recognizing extracellular signals, particularly specific small signaling molecules known as autoinducers. These quorum sensing signals are crucial for toxin production and virulence. This system also plays a role in the processes of sporulation and biofilm formation in this bacterium, which indicates the important role of this system. Considering the importance of toxin production in C. perfringens, vaccine strains and the limited studies that have been conducted so far. In this manuscript, the important role of the quorum sensing systems in the production and secretion of toxins in C. perfringens is investigated based on review of current studies. Finally, the results of the researches indicate that quorum sensing regulatory systems, including Agr and VirS/VirR two-component system, play an important role in regulating of the virulence genes expression in C. perfringens. Also, the role of autoinducer molecules in regulating of virulence genes and maintaining the balance of the intestinal microbiome will pave the way for the development of novel therapeutic targets to combat this pathogen. Overally, the regulation of gene expression in C. perfringens is complex and some toxin-producing genes cannot be considered as a completely separate system.