Abstract: Objective: To investigate the expression of MMP-1 and PTEN protein in basal cell papilloma (BCP), as well as their correlation with skin photoaging. Methods: Immunohistochemistry technique via Elivison method was employed to measure the expression of MMP-1 and PTEN protein in lesions from 50 cases of BCP on exposed areas, 50 cases on non-exposed areas, and 30 normal controls. We compared the differences among the three groups and analyzed the result. A total of 90 BCP cases on exposed areas were randomly divided into three groups. Titanium dioxide cream and placebo were respectively applied in the trial groups twice daily for 12 weeks, whereas the control group was non-administered. After 12 weeks, the MMP-1 in the lesions of the three groups was measured and compared. Results: The expression scores of MMP-1 on exposed areas were significantly higher than those in the control group (P < 0.01). No significant difference was found between non-exposed areas and the control group (P > 0.05). The expression scores of PTEN protein on exposed areas and on non-exposed areas were significantly lower than that in control group (P < 0.01). The expression scores of MMP-1 in the group that used titanium dioxide were evidently lower than those in control group after 12 weeks (P < 0.05). Conclusion: MMP-1 is overexpressed in BCP on exposed areas. PTEN protein is underexpressed in BCP of exposed areas and non-exposed areas. Skin photoaging is a possible cause of BCP on exposed areas.