To evaluate the expression of RECQL4 and its potential association with the clinical characteristics of HCC, we conducted a comprehensive next‐generation sequencing (NGS) analysis of tumor and matched adjacent non‐tumor tissues obtained from 159 patients with HCC at Fudan University Zhongshan Hospital (FDUZS cohort) as a training set and used three independent HCC datasets from public repositories for validation. This evidence concerns the gene RECQL4 and hepatocellular carcinoma.