There is a problem of non-uniformity response between multiple channels for a time-delayed integration (TDI) charge-coupled device (CCD) imaging system. Due to this problem, a correction method research based on radiometric calibration is conducted. A theoretical model for correction is deduced according to the flow of signal processing. A correction method is proposed based on weighted least square, which needs to acquire three sets of image data in 1/4, 1/2 and 3/4 saturation. Three sets of correction parameters are fitted by weighted least square using Gaussian weighting function to achieve the optimized parameters. The experimental verification is carried out using a TDI CCD imaging system. The results show that the photo response non-uniformity reduces from 4.09% to 0.85%, which is better than 1.93% obtained by two-point correction method. And it has a good performance in wide response range with advantages of high precision and good practicability. This method can be applied in many kinds of airborne or spaceborne camera payloads and lay the technical foundation to achieve high-quality remote sensing image data.