With the rapid development of sequencing technologies and sequenced genomes, single-nucleotide polymorphisms (SNPs) have become a common genomic tool in the study of biological diversity, genome variation, gene mapping, cloning, and marker-assisted selection. In this chapter, PCR-based SNP screening is discussed in detail. This includes preparation of solutions and buffers, designing of tetra-primers, PCR for DNA amplification, gel electrophoresis, and SNP screening. By grasping the techniques and experience from the wet laboratories, researchers can quickly use this genomic tool to tackle problems in their research.