Gallstones are one of the most common digestive system diseases and the prevalence of cholesterol stones is increasing year by year with people's lifestyle changes. The study of gallstones has gone deep into molecular biology. Research progress has been made in many aspects such as genetic inheritance epigenetics and cell signal transduction and it has become a current research hotspot. In this paper the origin of cholesterol gallstones is introduced in detail from the main lines of replication transcription and translation. Introduced from genetic inheritance the substitution of bases in the process of ABCG5 / G8 gene replication finally affects the translation of cholesterol transporter and finally affects the secretion of bile cholesterol. Insertion mutations in the ABCB4 gene have an effect on the translation of bile salt transporter and bile salt secretion. Epigenetics is mainly reflected in the influence of various microRNAs on the translation process. And the influence of various molecular signals in signal transduction on the translation process. The motor function of the gallbladder is an important reason for lithogenesis and genes such as the Cckar gene were found to regulate the movement of the gallbladder. In this paper the main lithogenic factors and mechanisms in genetic inheritance epigenetics and cell signal transduction will be expounded and the causes of cholesterol gallstones will be systematically expounded from the perspective of molecular biology.