Purpose: To investigate whether the early perfusion change in hepatocellular carcinoma (HCC) predicts the long-term therapeutic response to atezolizumab plus bevacizumab. Methods: We retrospectively selected 19 subjects (median age: 62 years, 4 females, and 15 males) having advanced HCC and treated with atezolizumab alone (n = 3) or in combination with bevacizumab (n = 16). The 4-phased CT or MRI imaging was performed for each subject before and at 9 ± 2 and 21 ± 5 weeks after therapy initiation. The tumor-to-liver signal ratio in the arterial phase was used to estimate the tumor perfusion. The change in tumor perfusion from the baseline to the 1st follow-up exam was correlated with the tumor response evaluated using mRECIST at the 2nd follow-up exam. The difference between favorably responding and non-responding groups was statistically analyzed using one-way ANOVA. Results: The mean tumor long axis in the baseline image was 59 ± 47 mm. The HCC perfusion changes were −26 ± 18% for complete (or partial) response (CR/PR, n = 8), −24 ± 12% for stable disease (SD, n = 8), and 9 ± 13% for progressive disease (PD, n = 3). The HCC perfusion change of the CR/PR groups was significantly lower than that of the PD group (p = 0.0040). The HCC perfusion changes between the SD and PD groups were also significantly different (p = 0.0135). The sensitivity and specificity of the early perfusion change to predict the long-term progression of the disease were 100 and 94%, respectively. Conclusion: The early change in HCC perfusion may predict the long-term therapeutic response to atezolizumab plus bevacizumab, promoting personalized treatment for HCC patients.