Fecal samples from participants aged 60–80 were collected and sequenced by a high-throughput second-generation sequencer to explore the structural composition of gut microbiota in elderly patients with hepatocellular carcinoma(HCC). Comparison of gut microbiota between patients with hepatocellular carcinoma and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance ofA Blautia,Fusicatenibacter,Anaerostipes, Lachnospiraceae_ND3007_group, CAG-56, Eggerthella, Lachnospiraceae_FCS020_group and Olsenellawere decreased significantly in the LC group. In contrast, the abundance ofEscherichia-Shigella, Fusobacterium, Megasphaera,Veillonella, Tyzzerella_4, Prevotella_2 and Cronobacterincreased significantly. The KEGG and COG pathway analyses showed that the dysbiosis of gut bacteria in primary liver carcinoma is associated with several pathways, including amino acid metabolism, replication and repair, nucleotide metabolism, cell motility, cell growth and death, and transcription. Age is negatively associated with the abundance ofBifidobacterium.Lachnospiraceae_ ND3007_ group,[Eubacterium]_hallii_group,Blautia,FuscatenibacterandAnaerostipesare negatively correlated with ALT, AST and GGT levels (p < 0.05), respectively. Alpha-fetoprotein (AFP) is positively associated with the abundance ofErysipelatoclostridium,Magasphaera,Prevotella 2,Escherichia-Shigella,Streptococcusand[Eubacterium]_eligens_group(p < 0.05), respectively. A random forest model showed that the generaEggerthella,Anaerostipes,andLachnospiraceae_ ND3007_ groupdemonstrated the best predictive capacity. The area under the Receiver Operating Characteristic Curve ofEggerthella,AnaerostipesandLachnospiraceae_ ND3007_ groupare 0.791, 0.766 and 0.730, respectively. These data are derived from the first known gut microbiome study in elderly patients with hepatocellular carcinoma. Potentially, specific microbiota can be used as a characteristic index for screening, diagnosis, and prognosis of gut microbiota changes in elderly patients with hepatocellular carcinoma and even as a therapeutic clinical target.