The invention provides tumor stem cell targeted lipid nanospheres. The tumor stem cell targeted lipid nanospheres are composed of A15-polyethylene glycol-octadecanol grafting, glycerin monostearate and salinomycin. Hydrophilic polyethylene glycol containing amino end groups and carboxyl end groups is linked with octadecanol through esterification reaction, and a long aliphatic chain segment of octadecanol can be inserted into lipid nanospheres, wherein A15 is an RNA aptamer, has strong affinity with CD133 molecules, and can target CD133 high expression liver tumor stem cells. The lipid nanospheres encapsulate the tumor stem cell specific drug salinomycin as a carrier, and salinomycin is delivered to tumor stem cells under the targeting action of A15 to realize the anti-tumor effect, so that CD133 high expression liver tumor stem cells can be targeted and treated.