The cholesterol solution concentration sensing characteristics based on tilted fiber Bragg grating (TFBG) are investigated by means of theoretical analysis and experiments. We prepare two groups of cholesterol solutions with the same concentration range and different refractive index ranges. The sensitivity of the two groups of solutions was 11.83 pm·mL/mg and 124.79 pm·mL/mg, respectively. The results show that the sensitivity of cholesterol solution can be improved by adjusting the refractive index range. This conclusion is valuable for measuring the concentration of fat-soluble solution.