[Abstract] Objective The aim of this study is to evaluate the differential diagnostic value of contrast-enhanced ultrasound (CEUS) for benign and malignant spleen lesions. Materials and Methods Clinical research reports of contrast-enhanced ultrasound(CEUS) differential diagnosis of splenic benign and malignant lesions were collected from Google scholar, PubMed, Embase, VIP database, WanFang database, CNKI during the time from establishment to March 10,2020. The two researchers screened the literature and extracted relevant information respectively and use QUADAS tool to evaluate the quality of all the included literatures. The software STATA 15.1 was used for statistical analysis. Results A total of 19 literatures (776patients, 875 lesions, 515 benign lesions and 360 malignant lesions) were included. The overall sensitivity of CEUS in the differential diagnosis of benign and malignant lesions of spleen was 0.97[95% CI: 0.91,0.99], the overall specificity was 0.91[95% CI: 0.87,0.93], the overall positive likelihood ratio was 10.5[95%CI: 7.7,14.4], the overall negative likelihood ratio was 0.04[95% CI: 0.01,0.10], the overall diagnosis ratio was 274 [95% CI: 96,781], and the area under the SROC curve was 0.96[95%CI:0.94,0.97], the sensitivity Q test P < 0.01, the I2 statistic was 65.63%, indicating the heterogeneity among the studies. The results of symmetry test were P = 0.01 and < 0.05, indicating the existence of publication bias. Conclusion Contrast-enhanced ultrasound (CEUS) is a valuable diagnostic method for benign and malignant lesions of spleen.