To get an in‐depth understanding of the mechanism regulating sorafenib sensitivity of HCC patients, we herein, for the first time, excavated the publicly available data of sorafenib‐sensitive (n = 21) and ‐insensitive tumor samples (n = 46) of HCC patients, and revealed that cofilin 1 (CFL1) is highly expressed in sorafenib‐insensitive HCC patients and closely correlated with the poor prognosis of HCC patients. Here, CFL1 is linked to hepatocellular carcinoma.