A rapid and sensitive assay to detect p53 mutations in urine has been developed for use in screening cancer patients. The method uses a locked nucleic acid (LNA) clamp mediated one-step PCR-based assay with a sensitivity of up to a single copy and can be used not only in urine, but also other biological samples. The assay is particularly useful for hepatocellular carcinoma, colon cancer, breast cancer, lung cancer, prostate cancer, ovarian cancer, bladder cancer, lymphoma, and stomach cancer.