Microfocus X-ray digital radiography (DR) offers high image resolution and is therefore well suited for the nondestructive inspection of small-diameter aero-engine tube welds. To optimize the inspection process parameters for microfocus DR applied to small-diameter aero-engine tube welds, a numerical model describing the relationship between process parameters and DR image quality was developed to guide parameter selection. First, a step wedge made of the same material as the aero-engine small-diameter tubes was used to simulate different X-ray penetration thicknesses of the workpiece. A quadratic regression model was then established to characterize the relationships between key process parameters (tube voltage, tube current, magnification, and penetration thickness, etc.) and DR image quality indexes (spatial resolution and contrast-to-noise ratio). Then, three small-diameter aero-engine tubes with different wall thicknesses were selected as representative workpieces, and the optimal sequence of process parameters was determined using a non-dominated genetic algorithm. Experimental results show that the measured DR image quality indices closely match the predicted values of the model, demonstrating that the proposed quadratic regression model can effectively predict the relationship between process parameters and DR image quality. Compared with conventional methods that adjust process parameters individually, the proposed method exhibits higher efficiency and stronger guidance and can be extended to similar DR inspection applications.