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Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers. The prognosis remains poor—the 5‑year overall-survival (OS) is 12–18%, all stages taken together. Systemic therapy has been limited to the use of tyrosine kinase inhibitors for more than a decade. Now immune therapy has also arrived in the field of systemic HCC treatment. Despite initial enthusiasm, the response rate to single agent immune checkpoint blockade (ICB) in HCC patients is approximately 15–20%. The immune tolerance of the liver and cirrhosis-associated immune dysfunction (CAID) may play a role in the immunological tumor escape phenomenon. The two phase 3 trials of pembrolizumab vs. placebo in second-line treatment (KEYNOTE-240) and nivolumab vs. sorafenib in first-line treatment (CheckMate 459) did not reach their primary endpoint of OS benefit. Pleasant news from IMbrave150 were recently published: the combination therapy of atezolizumab and bevacizumab reached significant benefit in overall response rate (ORR) and overall survival (OS) compared to current standard of care (SOC) sorafenib in patients advanced HCC in first-line therapy.