MicroRNAs (miRNAs) play important roles in development, differentiation, and homeostasis by regulating protein translation. In B-cell lymphoma, many miRNAs have altered expression levels, and for a limited subset of them, experimental data supports their functional relevance in lymphoma pathogenesis. This chapter describes an unbiased next-generation sequencing (NGS)-based high-throughput screening approach to identify miRNAs that are involved in the control of cell growth. First, we provide a protocol for performing high-throughput screening for miRNA inhibition and overexpression. Second, we describe the procedure for next-generation sequencing library preparation. Third, we provide a workflow for data analysis.