Background and Aims Hepatic perivascular epithelioid cell neoplasm (PEComa) is a rare primary tumor of the liver and is easily misdiagnosed as hepatocellular carcinoma and hepatic hemangioma due to the lack of specific symptoms and imaging features, which affects clinical treatment. To investigate the disease characteristics and treatment of hepatic PEComa, this study analyzed the clinical diagnosis and prognosis by summarizing the clinicopathologic data of previous patients with hepatic PEComa in our hospital to improve the diagnosis and treatment of this disease.Methods The clinicopathologic data of 38 patients with hepatic PEComa treated in Department of General Surgery, Xiangya Hospital, Central South University between July 2010 and June 2021 were reviewed, and the dataset that included clinical features, imaging manifestations, pathological features, treatment, and prognosis was analyzed.Results Of the 38 patients, 28 cases were (73.7%) females, and 10 cases (26.3%) were males, with a median age of 46 (21-66) years. A total of 40 liver nodules were detected in the 38 patients, and the size of lesions ranged from 1.0 to 20.0 cm, with a mean of (6.02±4.84) cm, among which 21 (52.5%) were located in the right liver, 17 (42.5%) in the left liver, and 2 (5%) in the caudate lobe. Ten patients presented with clinical symptoms such as abdominal distension and pain or chills with fever. Thirty-five patients underwent preoperative liver ultrasonography, and the lesions appeared as hyperechoic (18 cases), mixed echogenic (12 cases), or hypoechoic (5 cases) texture. Twenty-three patients underwent preoperative enhanced CT, and all lesions were enhanced in the arterial phase after enhancement. Nineteen presented hypointense in the portal and delayed phases, and 4 had a prolonged enhancement in the portal and delayed phases. Ten patients underwent magnetic resonance imaging examination, of whom, the lesion showed low signal intensity on T1-weighted images showed and high signal intensity on T2-weighted images in 6 cases, showed high signal intensity on T1 images and low signal intensity on T2 images in 3 cases, and showed equal signal intensity on both T1 and T2 images in one case; the lesions in all cases showed high signal on diffusion-weighted images. One patient underwent 18F-FDG PET/CT scan, on which low glucose metabolism and abnormally increased uptake of 18F-choline of the lesion was observed, and was misdiagnosed as hepatocellular carcinoma before operation. All patients underwent hepatectomy, including 2 cases, diagnosed with hepatic hemangioma and suffered rupture and bleeding after treatment with transcatheter arterial embolization in other hospitals. The lesions in all patients were diagnosed as hepatic PEComa by postoperative pathological examination. The positive rates of immunohistochemical staining for various tumor markers were 100% for HMB-45 (38/38), 47.4% for CD34 (18/38), 44.7% for melan-A (17/38), and 21.1% for SMA (8/38). Complete follow-up information was obtained in 34 cases of the 38 patients. The median follow-up time was 60.5 months. Only one case died 3 years after surgery, and no tumor recurrence or metastasis was observed in all the other patients during the follow-up period.Conclusion PEComa of the liver lacks specific clinical manifestations and imaging features, and postoperative histopathological examination is the gold standard for diagnosis. Surgical resection should be performed as early as possible for those with the development of symptoms and lesion challenging to be identified as benign or malignant.