The undetectable levels of TREX1 expression in hepatoma cells and efficient reduction of uncoated viral double-stranded DNA in hepatoma cells under the conditions of enhanced nucleocapsid disassembly by GLS4 treatment or replication of CpI126A mutant virus imply that one or multiple unknown cellular nucleases can digest uncoated viral DNA in the cytoplasm. This evidence concerns the gene TREX1 and hepatocellular carcinoma.