Liver cancer, or Hepatocellular Carcinoma (HCC), is one of the most common cancers in the world. Chronic infection with the hepatitis B virus (HBV) is one of the most critical factors that cause it. During chronic infection with HBV, variants of the virus are created. They may have deletion mutations in the PreS2 region. These variants may play a role in the occurrence of HCC. This study aims to determine the presence of these mutants in patients with liver cancer in China. For this purpose, virus DNA was extracted from the serum of 10 patients with HCC. After amplifying the PreS region and determining the sequence of this region from the genome, the presence of PreS2 mutants in these patients was investigated compared to the database. The results showed that a point mutation was observed at the level of the start codon of PreS2 in two samples. In three of the isolates, several amino acids were deleted at the end of the PreS2 region. In PreS2 deletion mutants, the T-cell and B-cell epitopes on the PreS2 region product are generally deleted. As a result, conditions are created where the virus can escape from the immune system. These mutant PreS2 proteins accumulate in the endoplasmic reticulum (ER) network and cause ER stress. In this way, in addition to creating unstable conditions in the cell genome, the proliferation of hepatocytes is stimulated indirectly. As a result, there is a possibility that the cells will progress toward becoming cancerous.