A thorough understanding of the thermo-mechanical coupling behavior during the interaction between pulsed laser and skin tissue is a prerequisite for successful application of pulsed laser technology in the treatment of various skin diseases and injuries. Taking into account the complex physiological structure of skin tissue, a theoretical model is established to characterize the thermo-mechanical response of multi-layer skin tissue with variable physical properties, in which the non-linear governing equations of bio-thermo-mechanics with dual-phase lag mechanism and Henrique burn equation are involved. The finite difference method was employed to obtain the time-space distribution of skin temperature, displacement and stress under repeated pulse laser action, and the incidental thermal damage was further evaluated on this basis. The numerical results stated that: i) repeated pulse laser can significant reduce the peak temperature of skin tissue and further reduce or even eliminate thermal damage under the premise of required energy threshold, ii) the thermo-mechanical coupling response and potential thermal damage will be inhibited when the temperature dependence of physical parameter is considered, in which the thermal stress is more sensitive to the temperature dependence than others, iii) the thermal damage is more sensitive to the input parameters than that of thermo-mechanical response, and the burn time can be effectively delayed or even avoided for appropriate input options.