Based on the mode coupling theory of a tilted fiber grating (TFBG), the spectral characteristics of a TFBG under different ambient refractive indexes are studied by the Optigrating software. The results show that when the ambient refractive index is less than the refractive index of the cladding mode, both the core mode and the cladding mode of the TFBG exist; in contrast, when the ambient refractive index is larger than or equal to the refractive index of the cladding mode, only the core mode exists and the cladding mode disappears. The experimental results of this TFBG in distilled water, anhydrous ethanol, safflower oil, peanut oil and soybean oil are consistent with the corresponding simulation results. These research results have certain guiding significance for the real-time leakage monitoring of pipelines full of liquids with larger refractive indexes.