Background In the global REACH-2 study, ramucirumab significantly improved overall survival (OS) compared with placebo in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP). REACH-2 China study aimed to evaluate the efficacy and safety of ramucirumab in Chinese patients with advanced HCC (NCT02435433). Methods REACH-2 China was a randomised, double-blind, placebo-controlled, phase 3 study done at 31 centres in China between Sep 16, 2015, and March 15, 2021. Patients with advanced HCC and AFP >= 400 ng/mL after first-line sorafenib were randomly assigned (2:1) to receive ramucirumab 8 mg/kg intravenously or placebo Q2W, until dis-ease progression or unacceptable toxicity. The primary endpoint was OS. Efficacy was assessed per intention-to-treat, and safety in patients who received any treatment. Findings Of 104 Chinese patients enrolled (44 in the global study and 60 in the China extension study), 70 received ramucirumab and 34 received placebo. Median OS was 9.1 months in the ramucirumab group and 6.2 months in the placebo group (HR = 0.854 [95% CI: 0.536, 1.359]). The most common grade 3 or worse treatment-emergent adverse event were hypertension (5 [7.1%] of 70 patients in the ramucirumab group vs 1 [2.9%] of 34 in the placebo group), pneumonia (5 [7.1%] vs 1 [2.9%]), and hyponatraemia (4 [5.7%] vs 0 [0%]). Interpretation Ramucirumab demonstrated clinically meaningful improvement in OS compared to placebo for Chi-nese patients with advanced HCC and elevated AFP, although lacking statistical superiority. Ramucirumab was well tolerated, with a manageable safety profile. The results are consistent with those of the global REACH-2 study, sup-porting a favourable risk-benefit profile for ramucirumab in this population. Funding Eli Lilly and Company, USA. Copyright (c) 2022 Eli Lilly and Company. Published by Elsevier Ltd. This is an open access article under the CC BY -NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)