This study explored the effects of fatty infiltration on the signal uncertainty of ultrasound backscattered echoes from the liver. Standard ultrasound examinations were performed on 107 volunteers. For each participant, raw ultrasound image data of the right lobe of liver were acquired using a clinical scanner equipped with a 3.5-MHz convex transducer. An algorithmic scheme was proposed for ultrasound B-mode and entropy imaging. Fatty liver stage was evaluated using a sonographic scoring system. Entropy values constructed using the ultrasound radiofrequency (RF) and uncompressed envelope signals (denoted by H R and H E , respectively) as a function of fatty liver stage were analyzed using the Pearson correlation coefficient. Data were expressed as the median and interquartile range (IQR). Receiver operating characteristic (ROC) curve analysis with 95% confidence intervals (CIs) was performed to obtain the area under the ROC curve (AUC). The brightness of the entropy image typically increased as the fatty stage varied from mild to severe. The median value of H R monotonically increased from 4.69 (IQR: 4.60-4.79) to 4.90 (IQR: 4.87-4.92) as the severity of fatty liver increased (r = 0.63, p < 0.0001). Concurrently, the median value of H E increased from 4.80 (IQR: 4.69-4.89) to 5.05 (IQR: 5.02-5.07) (r = 0.69, p < 0.0001). In particular, the AUCs obtained using H E (95% CI) were 0. 93 (0.87-0.99), 0.88 (0.82-0.94), and 0.76 (0.65-0.87) for fatty stages ≥mild, ≥moderate, and ≥severe, respectively. The sensitivity, specificity, and accuracy were 93.33%, 83.11%, and 86.00%, respectively (≥mild). Fatty infiltration increases the uncertainty of backscattered signals from livers. Ultrasound entropy imaging has potential for the routine examination of fatty liver disease.