In-flight absolute radiometric calibration is one of critical techniques for quantified information application of remote sensing. A novel calibration approach is presented based on reflected point sources. At the same time, the reflectance measurement on site is changed to accurate determination in laboratory. The top-of-atmosphere radiance of satellite-borne remote sensors can be calculated by simplified radiometric transfer code and measurement of the atmospheric optical properties. The calibration method can also isolate the response value of remote sensing image created by the targets from the response produced by sky path radiance and background radiance through in-flight point spread function estimation by point source method, which can eliminate the assumption of aerosol scattering properties. The approach can break the limit of time, locale and weather conditions at vicarious calibration sites and achieve high precision, high frequency mobile calibration for high spatial resolution satellite sensor in complex environments. Preliminary results show that its uncertainty is less than 3%. The difference of calibration coefficient is 3.02% between the proposed method and the method based on large-area gray-scale target. Simultaneously, the method can simplify the process and improve the calibration accuracy and efficiency.