Fourier—transform infrared (FT-IR) with digital subtraction method has been applied to investigate the molecular interactions of immiscible polystyrene (PS)/bisphenol A polycarbonate (PC) blends and miscible PS/tetra-methyl PC (TMPC) blends. The FT-IR results show that there are no interactions for PS/PC, and the miscibility of PS/TMPC blends is mainly due to the intermolecular interaction between the phenyl ring of PS and the carbonate group of TMPC. The phenyl ring band of PS is linearly shifted to higher wave number with increasing concentration of TMPC, and the bandwidth at half maximum intensity of the carbonyl band of TMPC is linearly decreased with increasing concentration of PS. The amplitude of the interactional bands is decreased with increasing temperature consistent with LCST behavior of the blend. The miscibility of PS/TMPC and immiscibility of PS/PC has also been discussed in terms of local free-volume, self-interactions, and intermolecular interactions based on the chemical structures of PC and TMPC. Furthermore, the immiscibility behavior for blends of methyl-substituted PS and TMPC, and blends of PS and halogen-substituted PC has been explained in terms of intra and intermolecular interactions caused by steric and/or induction effects.