Primary intrahepatic stones (PIS) is a refractory disease with a high incidence rate in southwest China, and some patients still require surgery again or even more times after initial treatment. Many studies in recent years have shown that some specific flora can colonize in the intrahepatic bile duct, leading to chronic infection and inflammation of the biliary system, and these specific types of flora, called "stone-causing flora", can produce metabolites such as β-glucuronidase and play an important role in the formation of pigmented stones. This article analyzes the role of stone-causing flora in the pathogenesis of PIS, so as to provide more treatment options for PIS patients.