Hepatocellular carcinoma (HCC) is one of the most life‑threatening diseases in the world. Members of the GTPase of the immunity‑associated protein (GIMAP) family are important in regulating apoptosis in cancer cells. However, the basic mechanism of GIMAP in HCC remains to be fully elucidated. The present study was performed to investigate the dysregulation of GIMAP family members in HCC. The techniques of polymerase chain reaction analysis, immunohistochemistry and ELISA were used to analyze the expression of GIMAP5 and GIMAP6 in HCC tissues, in matched noncancerous tissue samples, and in blood samples obtained from patients with HCC and healthy subjects. It was found that the mRNA expression levels of GIMAP5 and GIMAP6 were significantly downregulated in the HCC tumor samples, compared with the levels of expression in the matched non‑tumor tissue samples. Similarly, the mRNA expression levels of GIMAP5 and GIMAP6 were also significantly downregulated in the blood samples from patients with HCC, compared with the expression levels in the blood from healthy subjects. At the protein level, it was found that the GIMAP5 and GIMAP6 proteins were expressed at lower levels in the tumor tissue samples, compared with the matched normal tissue samples, and their expression levels were also lower in the blood samples from patients with HCC, compared with the blood samples from the healthy subjects. These data, demonstrating the downregulation of the mRNA and protein expression levels of GIMAP5 and GIMAP6 in the tumor tissues and blood of patients with HCC, suggested the involvement of GIMAP5 and GIMAP6 in the pathogenesis of HCC, and indicate their possible use as diagnostic markers for HCC.