To compare changes in skin sensitivity before and after treatment with a 1064-nm Q-switched Nd:YAG laser in healthy individuals, and to provide a reference for clinicians to use this laser reasonably. Nineteen healthy female volunteers underwent 10 random unilateral 1064-nm Q-switched Nd:YAG laser treatments. The skin transepidermal water loss rate (TEWL), skin glossiness, epidermal and dermal thickness and density, current perception threshold (CPT) value, facial blood perfusion were determined before and after treatment at different time points. Moreover, the changes in skin barrier function, blood vessels, and sensory nerve reaction in the treated and untreated sides of the face were recorded before and after treatment. Seventeen volunteers completed the 12-month follow-up study after 1064-nm Q-switched Nd:YAG laser treatment. At D3, M3, and M6, skin TEWL was decreased on the treated side of the face. Skin glossiness was significantly improved in the early post-treatment period (D1-D7) and M3, M6, and M12 compared with the untreated side of the face. There was no significant change in dermal and epidermal thickness or density at all time points before and after treatment. There were no significant differences in sensory nerve CPT values and local blood flow volume or velocity between the treated side of the face and the untreated side before and after treatment. Multiple low-energy 1064-nm Q-switched Nd:YAG laser treatments will not affect the barrier function of facial skin, skin nerve sensitivity, or local microcirculation of healthy skin over the long term. Therefore, 1064-nm Q-switched Nd:YAG laser treatment is safe, and does not alter skin sensitivity. Lasers Surg. Med. © 2021 Wiley Periodicals LLC. © 2021 Wiley Periodicals LLC.