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Background: Currently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC. Materials and methods: This was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab. All patients had liver MRE and liver biopsy at baseline and at 6 weeks of therapy. Change in HCC stiffness on MRE was compared with overall survival (OS), time to disease progression (TTP), and number of intratumoral CD3+ T lymphocytes. Analysis was performed using descriptive statistics and Spearman correlation (R); p-value < 0.05 was considered statistically significant. Results: Nine patients were evaluable. Median age was 71 years (range, 54–78). Etiology of liver disease was HCV (n = 4), HBV (n = 1) and NASH (n = 4). Median OS and TTP were 44 weeks and 13 weeks, respectively. Average baseline HCC stiffness and change in HCC stiffness were 5.0 kPa and 0.12 kPa, respectively. In contrast, average non-tumor liver stiffness was 3.2 kPa, and did not significantly change at 6 weeks (p = 0.42). Average size of measured tumor and change in size were 4 cm and − 0.32 cm, respectively. Change in HCC stiffness at 6 weeks correlated significantly with OS (R = 0.81), and TTP (R = 0.88,p < 0.01). Abundance of intratumoral T lymphocytes on tumor biopsy correlated significantly with HCC stiffness (R = 0.79,p = 0.007). Conclusion: Our pilot MRE data suggests early change in tumor stiffness may be an indicator of immunotherapy response in patients with advanced HCC. [ABSTRACT FROM AUTHOR]