To investigate the distribution of clay interlayers of the water conservancy hinge on the Yellow River, the Φ 615 mm large diameter diamond core drilling technology is researched and applied. As the largest diameter diamond core drilling in China currently, this technology is difficult and complex. In this paper, the parameters of drilling practice are discussed in detail, the drilling process is presented, and some common difficulties encountered are analyzed. Meanwhile the measures are proposed to solve these issues. The technology has yielded a good effect in practice and can be applied extensively.