The effects of well width, barrier height and strain on the refractive index of TE mode and TM mode of quantum well are analyzed and the physical mechanisms were dissected. The results show that for the polarization dependence of refractive index caused by quantum confinement effect of quantum well, the smaller the well width or the higher the barrier height, the larger the polarization dependence of refractive index. When the compressive strain increases, the polarization dependence of refractive index increases. Tensile strain can overcome the influence caused by quantum confinement effect, for quantum well structures with different well widths and barrier heights, there are suitable tensile strains to minimize the polarization dependence of refractive index. The smaller the well width or the higher the barrier height, the larger the tensile strain is required. Based on the above analysis, a design method is proposed to realize low polarization dependence of refractive index of quantum well and a quantum well In0.49Ga0.51As/In0.77Ga0.23As0.5P0.5 with low polarization dependence of refractive index (＜0.03) within C-band (1530~1565nm) is designed. The research result is helpful for the optimization design of some key devices in optical network.