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Simple Summary: The combination of atezolizumab and bevacizumab is a standard treatment for unresectable hepatocellular carcinoma. This study investigated the relationship between the gut microbiome and treatment efficacy. Fecal samples from 37 patients with hepatocellular carcinoma treated with this combination were analyzed. Patients were divided into responders (n = 28) and non-responders (n = 9). While overall microbiome diversity was similar, certain bacteria, such as Bacteroides stercoris and Parabacteroides merdae were more abundant in responders. Patients lacking these bacteria had worse prognoses. This suggests that differences in gut microbiota play a role in the effectiveness of atezolizumab and bevacizumab therapy. The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder (n = 28) and non-responder (n = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of Bacteroides stercoris and Parabacteroides merdae was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab. [ABSTRACT FROM AUTHOR]