Hepatitis B virus (HBV) causes liver cancer, which is the third most common cause of cancer-related death worldwide. Chronic inflammation via HBV in the host hepatocytes causes hepatocyte remodeling (hepatocyte transformation and immortalization) and hepatocellular carcinoma (HCC). Recognizing cancer stages accurately to optimize early screening and diagnosis is a primary concern in the outlook of HBV-induced hepatocyte remodeling and liver cancer. Genomic signatures play important roles in addressing this issue. Recently, machine learning (ML) models and bioinformatics analysis have become very important in discovering novel genomic signatures for the early diagnosis, treatment, and prognosis of HBV-induced hepatic cell remodeling and HCC. We discuss the recent literature on the ML approach and bioinformatics analysis revealed novel genomic signatures for diagnosing and forecasting HBV-associated hepatocyte remodeling and HCC. Various genomic signatures, including various microRNAs and their associated genes, long noncoding RNAs (lncRNAs), and small nucleolar RNAs (snoRNAs), have been discovered to be involved in the upregulation and downregulation of HBV-HCC. Moreover, these genetic biomarkers also affect different biological processes, such as proliferation, migration, circulation, assault, dissemination, antiapoptosis, mitogenesis, transformation, and angiogenesis in HBV-infected hepatocytes.