Pipe-in-pipe (PIP) flowlines have been widely arranged in offshore oil and gas fields for transportation, to achieve a significant thermal insulation capacity and outstanding resistance to external loads. However, the lateral indentation mechanisms of these multilayer pipelines are more complicated than those of single-layer pipelines. In this paper, the change and deformation laws of lateral indentation in the PIP structure were studied by experimental and numerical methods, and three stages of deformation behavior for PIP during lateral indentation were observed. The effects of the diameter and wall thickness of inner and outer pipes on the relationship between the indentation load and lateral indentation were also studied, which provided a reference for the design and analysis of PIP structures.