The touchdown zones of steel catenary risers and lazy wave risers are fatigue hotspots, where the risers interact continuously with the seabed due to hydrodynamic loading exerted on the host vessel. The whole-life interactions can range from small amplitude daily motion cycles to motions that involve large amplitude cyclic interaction with the seabed during storm events. A key design challenge that affects the fatigue life of these risers is the accurate modelling of the evolution of the riser-soil stiffness, throughout the whole-life of the riser and for different soil conditions, including overconsolidated conditions that may occur due to the geological history, aging or biochemical processes of the sediments. This paper describes centrifuge model pipe tests simulating whole-life riser-soil interaction in normally consolidated and uniform overconsolidated clay samples, under successive sequences of cyclic motions. Results confirm that the whole-life soil stiffness evolution depends strongly on cyclic amplitudes, with reconsolidation induced soil stiffness recovery after heavy remoulding, and is also influenced by the soil overconsolidation ratio, with a reduced tendency for soil hardening at higher soil overconsolidation ratios. This study provides insights into the relevant cyclic soil stiffness to consider when assessing the whole-life design of risers interacting with overconsolidated seabed sediments.