We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients.<h4>Results</h4>In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton.<h4>Conclusions</h4>The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. The gene discussed is ACTN1; the disease is hepatocellular carcinoma.