We found that knockdown of AKT1S1, TBL1Y, SKAP2, and AMPD2 significantly induced apoptosis in HCC cells only in the presence of Sorafenib, suggesting these genes were also involved in Sorafenib resistance and the result from CRISPR/Cas9 knockout library screening could be recapitulated (Fig. S2a). The gene discussed is AKT1S1; the disease is hepatocellular carcinoma.