Nodular Regenerative Hyperplasia (NRH) of liver is a rare benign primary liver disease in clinical practice. The pathogenesis is considered to be reactive hyperplasia of liver cells in response to hepatic microvascular injury, and most of NRH are considered to be related to autoimmune diseases, drugs, infections, etc. The NRH features showed diffuse nodular changes in liver parenchyma without fibrotic changes, or solitary nodules in liver. Clinically, it is often misdiagnosed as cirrhosis with regenerative nodules, hepatic adenoma, and Focal Nodular Hyperplasia (FNH) of the liver. In the background of specific liver disease, it is even easily misdiagnosed as malignant liver tumors, such as Hepatocellular Carcinoma (HCC). At present, Although the knowledge and detection rates of NRH have increased in clinical, the published articles are still dominated by case reports, and there is no report on the relationship between NRH and hepatolithiasis. This study reports the case of a 59-year-old female patient admitted to our hospital because of multiple intrahepatic and extrahepatic bile duct stones accompanied by obstructive cholangitis, and found a huge Nodular regenerative hyperplasia of liver. The patient recovered well after Endoscopic Retrograde Cholangiopancreatography (ERCP) to relieve bile duct obstruction, and was advised to follow up the liver mass in a specialist outpatient clinic after discharge to prevent NRH complications.