Purpose: This in vitro study evaluated the effects of surface treatments and thermocycling on the bonding of autopolymerizing silicone soft denture liner (Sofreliner) to denture base resin. Materials and Methods: The bonding surfaces of denture base cylinders were polished with 600-grit silicon carbide paper and pretreated with applications of Sofreliner Primer, Sofreliner Primer after air abrasion, Reline Primer, or Reline Primer after air abrasion. Failure loads and elongation at failure were measured after subjecting specimens to 0, 10,000, 20,000, and 30,000 thermocycles. Failure modes were assessed for all specimens. Seven specimens were fabricated for each of 16 groups, including four pretreatments and four thermocycle groups. Results: Failure loads of the Sofreliner Primer group were significantly higher than those of the air-abrasion group up to 20,000 thermocycles; both groups showed cohesive failures of the soft denture liner. Failure loads of the Reline Primer group were significantly higher than with Reline Primer after air abrasion up to 10,000 thermocycles. Failure mode after 10,000 thermocycles was cohesive for the Reline Primer group and mixed cohesive/adhesive for Reline Primer after air abrasion. Failure loads of the Sofreliner Primer group were significantly higher than those of the Reline Primer group at each thermocycling interval. Elongation values decreased after 10,000 thermocycles for all groups. Conclusion: Air abrasion on the denture base resin surface was not effective in enhancing failure load. Cyclic thermal stress is one factor degrading the bond between soft denture liner and acrylic resin denture base.