Hepatocellular carcinoma (HCC) is a representative of almost 85-90% of liver cancer in the recent global incidence. HCC is the second leading cause of mortality in subjects with cancer. The higher prevalence of this disease significantly increased in the Asia Pacific region in the last decades. Fatty liver (steatosis) linked cirrhosis showed a substantial contribution to the acceleration of HCC in patients. Importantly, another primary inducer of fatty liver, a short non-coding RNA miR-122, and miR196a are the essential miRNAs that predicted enhance the progression of HCC in the younger age. However, the lack of information about HCC related liver-derived hormone and miRNA remains. This study was conducted by using miR-122+/--miR-196 (+) to generate miR-122-/--miR 196 (+). In the current data, the significant morphological alteration of the liver with the early formation of nodule-like in the surface area was observed. Based on the histological section, the chronic portal inflammation also occurred in the liver of this double genetic modification mouse model. In summary, the interaction of miR-122 and miR196a may accelerate liver fibrosis due to chronic inflammation within the liver progress to cirrhosis in the early stage of hepatocellular carcinoma.