The present study examines the cumulative effects of sub-erythema application of squalene-monohydroperoxide (Sq-OOH), the initial products of UV-peroxidated squalene, to the skin of hairless mice. Sq-OOH was isolated by the methanol extraction and preparative HPLC method. Repeated topical application of 10 mM Sq-OOH to hairless mice for 3 weeks induced definite skin roughness and crinkle formation. 3-D surface parameter analysis revealed changes in all roughness parameters (number of furrows and crests, distance between a furrow and next crest, and irregularity) of the group treated with more than 3 mM Sq-OOH compared to the control group. These skin surface changes were not induced by squalene, squalene-monohydroxide (Sq-OH) or organic hydroperoxides such as tert-butyl hydroperoxide and cumene-hydroperoxide at 10 mM. Similarly, such changes were not induced by primary irritants, such as sodium lauryl sulfate and n-tetradecane under the same experimental conditions. Skin conductance decreased, following application of 10 mM Sq-OOH. Histological observation revealed that application of 10 mM Sq-OOH induced slight hyperkeratosis, moderate epidermal thickening and slight hyperplasia of sebaceous glands.