In this paper, an optical fiber Fabry–Pérot (FP) microfluidic sensor based on the capillary fiber (CF) and side illumination method is designed. The hybrid FP cavity (HFP) is naturally formed by the inner air hole and silica wall of CF which is side illuminated by another single mode fiber (SMF). The CF acts as a naturally microfluidic channel, which can be served as a potential microfluidic solution concentration sensor. Moreover, the FP cavity formed by silica wall is insensitive to ambient solution refractive index but sensitive to the temperature. Thus, the HFP sensor can simultaneously measure microfluidic refractive index (RI) and temperature by cross-sensitivity matrix method. Three sensors with different inner air hole diameters were selected to fabricate and characterize the sensing performance. The interference spectra corresponding to each cavity length can be separated from each amplitude peak in the FFT spectra with a proper bandpass filter. Experimental results indicate that the proposed sensor with excellent sensing performance of temperature compensation is low-cost and easy to build, which is suitable for in situ monitoring and high-precision sensing of drug concentration and the optical constants of micro-specimens in the biomedical and biochemical fields.