Background: Skin cancer belongs to the most frequent types of malignancies, that actually constitutes an important public health concern. Oxidative stress is an essential element and probably a driving factor for many chronic diseases, encompassing diabetes, Alzheimer and cancer. Malondialdehyde (MDA), Catalase (CAT) and superoxide dismutase (SOD) considered the most widely employed biomarkers for oxidative stress. Aim of the study: To assess the oxidative stress imbalance between tumor and normal tissues in Egyptian patients, suffering from skin cancer. Patients and method : The present study is regarded as a pilot case-control study constituting twenty skin tumor tissues and their adjacent normal tissues extracted from patients with human basal cell (BCC) and squamous cell (SCC) carcinomas, so as to evaluate the difference in the levels of MDA, CAT and SOD biomarkers between normal and cancer tissues, using a spectrophotometry method. The P-value is considered significant if its value is less than 0.05. Results : Tumor tissues had mean MDA levels of 1256±391.6 nmol/ml, which are higher than normal tissues' mean values 828.5± 117.8 nmol/ml. However, the mean SOD level of tumor tissue was decreased (100.6 ± 16.66 nmol/ml) compared to normal tissues (174.2± 14.69 U/L). With a P-value <0.05, the mean CAT level was lower in tumor tissue (101.0 ± 21.92U/L) than in normal tissues (182.9± 17.52ng/ml). Conclusion: MDA, SOD and CAT levels could be utilized as significant predictors or screening tests for detecting the population more likely to develop certain forms of skin cancer.