When conducting large-scale cohort studies, numerous statistical issues arise from the range of study design, data collection, data analysis and interpretation. In genomic cohort studies, these statistical problems become more complicated, which need to be carefully dealt with. Rapid technical advances in genomic studies produce enormous amount of data to be analyzed and traditional statistical methods are no longer sufficient to handle these data. In this paper, we reviewed several important statistical issues that occur frequently in large-scale genomic cohort studies, including measurement error and its relevant correction methods, cost-efficient design strategy for main cohort and validation studies, inflated Type I error, gene-gene and gene-environment interaction and time-varying hazard ratios. It is very important to employ appropriate statistical methods in order to make the best use of valuable cohort data and produce valid and reliable study results.