Abstract Background Genome-wide association studies (GWAS) have identified common genetic risk variants in many loci associated with multiple cancers. We sought to systematically evaluate the utility of these risk variants in identifying high-risk individuals for eight common cancers. Methods We constructed polygenic risk scores (PRS) using GWAS-identified risk variants for each cancer. Using data from 400,812 participants of European descent in a population-based cohort study, UK Biobank, we estimated hazard ratios associated with PRS using Cox proportional hazard models, and evaluated the performance of the PRS in cancer risk prediction and their ability to identify individuals at an over 2-fold elevated risk, a risk level comparable to a moderate-penetrance mutation in known cancer predisposition genes. Results During a median follow-up of 5.8 years, 14,584 incident cases of cancers were identified (ranging from 358 epithelial ovarian cancer cases to 4,430 prostate cancer cases). Compared with those at an average risk, individuals among the highest 5% of the PRS had a 2 to 3-fold elevated risk for cancer of the prostate, breast, pancreas, colon/rectum, or ovary, and an approximately 1.5-fold elevated risk of cancer of the lung, bladder or kidney. The areas under the curve ranged from 0.567 to 0.662. Using PRS, 40.4% of the study participants can be classified as having an over 2-fold elevated risk for at least one site-specific cancer. Conclusion A large proportion of the general population can be identified at an elevated cancer risk by PRS, supporting the potential clinical utility of PRS for personalized cancer risk prediction.