In fluorodeoxyglucose (FDG) positron emission tomography (PET)/computerized tomography (CT) studies, physiological liver FDG uptake has been used as a reference in the evaluation of FDG uptake in pathological processes, even in malignancies. There is an ongoing debate on the effect of liver attenuation and FDG uptake in the liver. We aimed to evaluate the possible effect of fatty infiltration on the standardized uptake value (SUV) of the liver. Methods: A total of 88 patients were included in this study. Subjects were divided into 2 groups by calculating the Hounsfield unit (HU) of the liver from the unenhanced CT part of the PET/CT study and comparing it with that of the spleen. Fatty liver group included 42 patients (26 female, 16 male) with a mean age of 59.6±11.6 years, while control group consisted of 46 patients (22 female, 24 male) with a mean age of 60.2±11 years. The patients with a mean liver attenuation value (in HU) equal and greater than that of spleen were enrolled in the control group, while the patients with a mean liver attenuation value lower than the spleen were included in the fatty liver group. A subset of patients in the fatty liver group with difference in attenuation between the liver and spleen of more than 10 HU (HUS-HUL >10) were evaluated separately. Age, weight, history of diabetes mellitus (DM) and chemotherapy, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, simultaneous blood glucose levels during PET scan and the elapsed time between FDG injection and the beginning of PET scan were recorded. Results: The average SUVmean and SUVmax values were 2.7±0.7 and 3.6±0.9 in the fatty liver group, 2.8±0.7 and 3.8±1 in the HUS-HUL >10 group and 3.3±0.6 and 4.4±0.9 in the control group, respectively. The average SUVmean and SUVmax values of the fatty liver group and HUS-HUL >10 group were significantly different from the control group (p<0.05). The patients in the fatty liver group had higher ALT (p=0.025) and glucose levels (p=0.001), weight (p=0.001), and DM rate (p=0.002) compared to the control group. Conclusion: Hepatic steatosis causes a statistically significant decrease in SUVmean and SUVmax values in liver. Therefore, we must be careful when using the liver as an internal reference organ