Objective To analyze the value of ultrasound contrast and enhanced CT in the diagnosis of alpha fetoprotein (AFP)-negative hepatic space-occupying lesions. Methods A total of 57 cases of patients with AFP-negative hepatic space-occupying lesions treated in our hospital from November 2015 to October 2017 were selected for the study and were given ultrasound contrast and enhanced CT. Surgical pathology was used as the gold standard, and the diagnostic values of ultrasound contrast and enhanced CT were compared in the diagnosis of AFP-negative hepatic space-occupying lesions. Results The beginning enhancement time, beginning reduction time and transition time of ultrasound contrast in hepatic malignant lesions were all significantly different from those in benign lesions and surrounding liver parenchyma (P<0.05). The sensitivity, specificity and accuracy in detecting AFP-negative hepatic space-occupying lesions were 87.18%, 94.44%, and 89.47% respectively by ultrasound contrast and were 82.05%, 88.89% and 84.21% respectively by enhanced CT. Conclusion Ultrasound contrast and enhanced CT both have a certain diagnostic value for AFP-negative hepatic space-occupying lesions.