Background: Calcium oxalate kidney stone is one of the common diseases in the urinary system and has a high recurrence rate. Currently, the pathogenesis of kidney stone and the methods to prevent recurrence are still being investigated. Autophagy, as an event of cellular self-repair, has received attention in the field of kidney stone in recent years. In some current studies, autophagy has shown destructiveness and protectiveness in the pathogenesis of kidney stone. The inhibition or promotion of autophagy may be a key target for future kidney stone therapy. This systematic literature review discusses the function of autophagy in kidney stone pathogenesis in the context of current research and synthesizes the evidence analysis to provide a basis for new future therapies. Method: We systematically reviewed the literature during September 2021 according to the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) guidelines. Articles on studying the role of autophagy in the pathogenesis of calcium oxalate kidney stone were extracted from PubMed, MEDLINE, Embase and Scopus, including in vivo versus in vitro experiments. The study topic, language and publication date were not restricted. Two authors (Li and Zhou) searched and screened the literature. Results: We screened 18 articles from the 33 collected articles, of which 6 conducted in vitro cellular studies, four conducted animal studies, eight conducted cellular studies with animal studies, and five studied human specimens. In early studies, the literature generally concluded that autophagy is deleterious in the development of kidney stone. In 2020, the idea of the protectiveness of autophagy associated with kidney stone was first proposed and focused on targeting transcription factor EB. In addition, the interaction of autophagy with other cellular events and the regulation of signaling molecules are focused on in this paper. Conclusion: This systematic review provides advances in research on the role of autophagy in renal calculi. The current studies suggest that both upregulation and downregulation of autophagy may ameliorate injury in kidney stone models. The authors prefer the upregulation of autophagy as a future research direction for kidney stone treatment.