Objective This study aimed to explore the clinical value of ultrasound guide core needle biopsy（USG-CNB） in the diagnosis of lymphoma.To further explore the clinical value of USG-CNB in the diagnosis of lymphoma in different lesions.Methods The clinical data of 353 patients with lymphoma who underwent USG-CNB and surgical excision biopsy (SEB) in our hospital were analyzed retrospectively. Among them，there were 139 cases of the USG-CNB group，214 cases of the SEB group.Combined with clinical manifestations, laboratory examination, imaging examination, pathological examination and drug treatment effect, the final diagnosis was obtained as the gold standard for diagnosis, the diagnostic efficacy of USG-CNB for short-diameter lymphoma of different lesions was compared, and the diagnostic efficacy of USG-CNB and SEB for different subtypes (Hodgkin's lymphoma and non-Hodgkin's lymphoma) and site lymphoma was compared.Results The diagnosis was successful in 117 cases in the USG-CNB group and 202 cases in the SEB group, and the diagnostic accuracy between the two groups was compared (84.2% vs. 94.4%), and the difference was statistically significant (P = 0.003). There was no significant difference in the diagnostic accuracy of short-diameter lymphoma with different lesions in USG-CNB group. The diagnostic accuracy of USG-CNB and SEB in Hodgkin's lymphoma was compared (50% vs. 100%), the difference was statistically significant (P ＜ 0.001). There was no significant difference in the diagnostic accuracy of non-Hodgkin's lymphoma (88.6% vs. 93.8%).There was a significant difference in the diagnostic accuracy between USG-CNB and SEB for superficial lymphoma (83.0% vs. 93.5%) (P = 0.001). There was no significant difference between USG-CNB and SEB in the diagnosis of deep lymphoma (87.9% vs. 96.6%). There was no significant difference between USG-CNB and SEB in the diagnosis of superficial and deep non-Hodgkin's lymphoma.Conclusion The application of USG-CNB in the diagnosis of lymphoma has the advantages of real-time, rapid, minimally invasive and cheap ,especially for lymphoma lesions located in the deep part.