Gain calibration for X-ray imaging systems with a movable flat panel detector and an intrinsic crosshair is a challenge due to the geometry-dependent heel effect and crosshair artifact. This study aims to develop a gain correction method for such systems by implementing the Multi-Acquisition Gain Image Correction technique. Flood field images containing crosshair and heel effect were acquired in 4 different flat panel detector positions at fixed exposure parameters. The crosshair region was automatically detected using common image processing algorithms and removed by a simple interpolation procedure, resulting in a crosshair-removed image. A large kernel-based correction was then used to remove the heel effect. Mask filters corresponding to each crosshair region were applied to the resultant heel effect-removed images to invalidate the pixels of the original crosshair region. Finally, a seamless gain map was composed with corresponding valid pixels from the processed images either by the sequential replacement or by the selective averaging techniques developed in this study. Quantitative evaluation was performed based on normalized noise power spectrum and detective quantum efficiency improvement factor for the flood field images corrected by the MultiAcquisition Gain Image Correction-based gain maps. For comparison purposes, a single crosshair-removed gain map was also tested. As a result, it was demonstrated that the Multi-Acquisition Gain Image Correction technique achieved better image quality than the crosshair-removed technique, showing lower normalized noise power spectrum values over most of spatial frequencies. The improvement was more obvious at the priori-crosshair region of the gain map. The mean detective quantum efficiency improvement factor was 1.09 + 0.06, 2.46 + 0.32, and 3.34 + 0.36 in the priori-crosshair region and 2.35 + 0.31, 2.33 + 0.31, and 3.09 + 0.34 in the normal region, for crosshair-removed, Multi-Acquisition Gain Image Correction-sequential replacement, and Multi-Acquisition Gain Image Correction-selective averaging techniques, respectively. Therefore, this study indicates that the introduced Multi-Acquisition Gain Image Correction technique is an appropriate method for gain calibration of an imaging system associated with a moving flat panel detector and an intrinsic crosshair.