The axial friction response of subsea pipelines in soft clays is a very important aspect for designers of subsea pipelines but the response is not well understood so far. There is a pressing need for the comprehension of the response. In this paper, model tests are performed using full-scale pipes coated with polyethylene (PE) to study the effects of the set-up period, the pipe diameter, the buried depth of the pipe, the shear strength of soft clays and the loading rate on the axial friction response of pipelines in soft clays. The variations of the axial friction coefficient are analyzed using the effective stress method based on model test results. The results show that the axial friction resistance increases with the increasing pipe diameter but the effect of the pipe diameter on the axial friction coefficient can be neglected. The ultimate axial resistance also increases with the increase of the buried depth of pipelines, the undrained shear strength of soft clays and the loading rate. The axial friction coefficient increases with the increasing loading rate. However, the axial friction coefficient decreases with the increasing buried depth. The method to determine the axial friction coefficient is developed by analyzing model test results, which considers the effects of the diameter, the buried depth, the undrained shear strength of soft clays and the loading rate. The study results not only extend the industry data base but also supply a basis to determine the axial friction coefficient of PE-coated pipes in soft clays for ocean engineering geological investigations.