Background: Hepatocellular carcinoma (HCC) is the fourth most common cancer-related cause of death worldwide and poses a severe threat to public health. In addition to being an underlying risk factor for HCC, obesity is one of the common causes of metabolic-associated fatty liver disease (MAFLD). Objective: Therefore, the current study aimed to investigate the expression levels of both circARF3 (ADP-ribosylation factor 3) and its target gene miR-103 in obese patients with MAFLD and to assess their relations to susceptibility and clinicopathological features of HCC. Patients and methods: The current study was conducted on 100 subjects (50 control groups and 50 obese patients with MAFLD). The case group was subclassified to 39 patients without HCC and 11 patients with HCC. The expression levels of circARF3 and miR-103 were investigated by RT PCR. Resultsː Our results revealed statistically significant higher values of circARF3 in MAFLD (1.89±0.614) compared to control (0.72±0.341). In addition, the level of miR-103 was statistically significantly higher in MAFLD (2.41±0.82) compared to control (0.912±0.335), P ˂0.001. Also, there were statistically significant higher values of circARF3 in HCC (4.67±1.63) compared to non-HCC (1.44± 0.74). In addition, the level of miR-103 was statistically significantly higher in HCC (4.99±1.32) compared to non-HCC (1.512±0.45), P <0.001. Interestingly, circARF3 and miR-103 significantly correlated with obesity indices and metabolic and hepatic dysfunction biomarkers. Cut-off values 0.94, 1.2, 1.8, 2.98 were able to discriminate simple steatosis, steatohepatitis, cirrhosis, and HCC with AUC 0.78, 0.64, 0.77, 0.81 respectively. Conclusionsː The current study results detected upregulation of both studied epigenetic markers; circARF3 and miR-103 in obese MAFLD patients especially patients with HCC. Thus, they could be used as diagnostic biomarkers of MAFLD-associated HCC.