The influence of encapsulation with caseins on the stability of cyanidin 3-O-glucoside (C3G) was investigated. The modified casein nanoparticles (MCs) prepared at pH 5.5 after heated at 80 °C for 30 min was applied to encapsulate C3G. The diameter of nanoparticle (MCs-C3G) was 110 ± 0.31 nm and zeta-potential was −8.83 ± 0.52 mV. The molecular weight of α-casein (32 kDa) and β-casein (25 kDa) increased along with the encapsulation of C3G. The interactions of MCs with C3G were examined at pH 6.3 by fluorescence spectroscopy and IR spectroscopy. MCs encapsulated C3G mainly via the hydrophobic interaction. The secondary structures of caseins were changed along with the combination of C3G, with a decreasing in α-helix, turn random, and coil structure, as well as increased β-sheet. In addition, the MCs-C3G interaction appeared to have a positive effect on the thermal, oxidation and photo stability of C3G.