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Background It remains essential for patient safety to develop non-invasive diagnostic tools to diagnose non-alcoholic fatty liver rather than invasive techniques. Aim Our case-control study was to address the value of circulating miRNAs as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases (NAFLD) and monitoring of disease progression. Methods Routine clinical assessment, laboratory tests, anthropometric study, and liver biopsy results reported for 210 patients with NAFLD (124 patients of simple steatosis (SS) and 86 of non-alcoholic steatohepatitis (NASH)). Apparently matched for age and gender, healthy participants (n= 90) were enrolled as a control group. Serum samples were tested for micro-RNAs (−122, −34a and −99a) by quantitative-PCR. Results By histopathology, 124 of the NAFLD group were of SS and 86 patients were of NASH. Compared with the control subjects, both mi-RNA-122 and −34a levels were increased in NAFLD (p< 001) and at a cut-off = 1.261, mi-RNA-122 had 92% sensitivity, 85% specificity to differentiate NAFLD from healthy controls, while mi-RNA-99a were significantly decreased in NAFLD patients with an observed decrease in disease severity, and at a cut-off = 0.46, miRNA-99a had 94% sensitivity and 96% specificity to discriminate SS from NASH. Conclusion The integration of a circulating mi-RNA panel to diagnose NAFLD cases and to discriminate between SS and NASH. Large-scale study is still needed to verify the other mi-RNA profiles and their role in NAFLD pathogenesis and targeting therapy.