We demonstrated herein a kind of thermal and oxidation dual responsive polymer with novel structure of alternating hydrophilic and hydrophobic segments in the backbone. The polymers were facilely synthesized by thiol-ene polymerization of poly(ethylene glycol) diacrylate (PEGDA) and 1,2-ethanedithiol (EDT) monomers. The resultant PEG-EDT copolymers exhibited sharp and reversible thermal-induced phase transition in aqueous medium which was identified to be caused by the cooperativity of dehydration of PEG segments and increased hydrophobic interaction between β-thioether ester segments in the backbone. Additionally, the cloud point temperatures of PEG-EDT copolymers were examined to be dependent on the molecular weight of PEG, polymer concentration, addition of NaCl and isotopic solvent. More importantly, the PEG-EDT copolymers were tested to be oxidation sensitive due to the presence of oxidizable thioether groups in the backbone. The collapsed polymers at elevated temperature could be easily turned into completely water-soluble polymers by oxidative conversion of hydrophobic thioether groups into hydrophilic sulfoxide and sulfone groups. This oxidation-switchable water solubility inspired us to use this copolymer in design of oxidation-triggered drug delivery system. Thus, a triblock copolymer mPEG-b-575EDT-b-mPEG was synthesized by a one-pot method. The resulting triblock copolymer could self-assemble into nanoparticle using thermal and oxidation dual responsive 575-EDT as the core and mPEG as the shell. As a consequence, the hydrophobic model drug (i.e., Nile Red) can be effectively encapsulated into the collapsed nanoparticle core at body temperature while released by oxidation-triggered disruption of the nanoparticles. This tunable thermo-responsive behavior in combination with oxidation-triggerable thioether groups makes these PEG-EDT copolymers promising for reactive oxygen species (ROS) responsive drug delivery.