Objective To compare the effect of various methods for securing a nephrostomy tube through a orthogonal design. Methods One end of a 14Fr silicone nephrostomy tube was fixed on the polyethylene display board, and the other end on the display force card. The fixation material, fixation method and area were seen as 3 influencing factors, and each factor had 3 levels. Three experiments were conducted in each group (factor) and the average value of pulling forces was calculated as the final tension value F. A total of 27 experiments were conducted in 9 fixation schemes.L9 (33) orthogonal experimental matrix was used to study the effects of different materials (medical adhesive paste, medical breathable tape, medical non-woven tape), fixation methods (cross fixation, I-shaped fixing method, modified I-shaped fixing method) and fixation areas (16 cm2, 24 cm2, 32 cm2) on the fixation strength of the nephrostomy tube. Results Among the 3 factors selected in the orthogonal experiment, the order of significance in terms of tension value was:material > method > area; among the three kinds of fixation materials, medical adhesive paste had the highest fixation strength. Conclusion The best fixation plan for a nephrostomy tube is to use medical adhesive paste and modified I-shaped fixation method. This could provide a reference for selection of tube fixation scheme in clinical settings.