Mesoporous silica core-shell nanospheres encapsulating a rare-earth metal complex (RC) were first synthesised through a facile W/O (water in oil) inverse microemulsion method. In order to achieve targeted complex delivery, folic acid (FA) was used as the targeting component due to its high affinity for over-expressed folate receptors (FRs) in cancer cells. The RC2@SiO2-FA nanospheres were characterised via ultraviolet-visible light absorption spectroscopy (UV-vis spectroscopy), dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A microwave method was used to synthesise five RC cores based on 4-chlorophenoxyacetic acid, and their crystal structures were further confirmed using X-ray diffraction. The five RC cores have the following chemical formulae: [Er2(p-CPA)6(H2O)6] RC1, [Ho2(p-CPA)6(H2O)6] RC2, [Sm(p-CPA)3(H2O)] RC3, [Pr(p-CPA)3(H2O)]·3H2O RC4 and [Ce(p-CPA)3(H2O)2]·2H2O RC5. The carboxyl groups showed two kinds of coordination modes, namely μ2-η1:η1 and μ2-η1:η2, among RC1-RC5. The flexible -OCH2COO- spacer group, which can undergo rotation of its C-O and C-C bonds, offered great potential for structural diversity. In vivo experiments revealed that the nanospheres exhibited no obvious cytotoxicity on HepG2 cells and 293 T cells, even at concentrations of up to 80 μg mL-1. Nevertheless, all of the RC cores showed a certain degree of anti-tumour efficacy; in particular, RC2 showed the strongest cytotoxicity against HepG2 cells. Interestingly, the cytotoxicity of all of the RC2@SiO2-FA nanospheres was higher than that of lone RC2. These types of FA-targeted mesoporous silica nanocarriers can be used for the delivery of anti-tumour RC, and provide a basis for the further study of affordable non-platinum-based complexes.