More importantly, considering the toxic and side effects of sorafenib[7, 21] and the great potential of nucleic acid drugs (e.g., siRNA and mRNA) on cancer therapy,[3, 22] we further constructed a reduction‐responsive nanoparticle (NP) platform to systematically co‐deliver CFL1 siRNA (siCFL1) and sorafenib, and demonstrated that this co‐delivery system could effectively enhance the sorafenib sensitivity of HCC cells via silencing CFL1 expression and significantly inhibit HCC tumor growth. Here, CFL1 is linked to neoplasm.