The invention belongs to the technical field of biological medicine, and discloses a novel albumin-siRNA composite nanometer particle, and a preparation method and applications thereof. According to the preparation, the internal space structure of albumin is destroyed using a disulfide bond reducing agent, and proteins containing mercapto group active groups are obtained, siRNA and/or a modified substance SH-siRNA is added, and a selenium compound is added so as to obtain the novel albumin-siRNA composite nanometer particle. The preparation method is simple; the nanometer size is uniform at different dilution concentrations, the dispersion performance is excellent, the stability in artificial gastric juice, intestinal juice, and blood environment is excellent; and in addition, the novel albumin-siRNA composite nanometer particle possesses intracellular reduced glutathione microenvironment responsiveness; the novel albumin-siRNA composite nanometer particle possesses oral administrationand injection administration living tumor targeting characteristic, is capable of increasing siRNA anti-cancer drug oral administration or injection administration anti-cancer activity, and reducingtoxic or side effect.