We hypothesized that the LTX/siR‐NPs could enhance the antitumor activity of LTX‐315 and the siRNA upon systemic administration, and consequently upregulate the components associated with T and NK cell recruitment and activation as well as effectively suppress TGF‐β1 secretion by tumor cells, shaping an immunologically “hot” tumor with high infiltration of lymphocytes. Here, TGFB1 is linked to neoplasm.