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The rational design of novel molecules with desired bioactivity is a critical but challenging task in drug discovery, especially when treating a novel target family or understudied targets. Here, we propose PGMG, a pharmacophore-guided deep learning approach for bioactivate molecule generation. Through the guidance of pharmacophore, PGMG provides a flexible strategy to generate bioactive molecules with structural diversity in various scenarios using a trained variational autoencoder. We show that PGMG can generate molecules matching given pharmacophore models while maintaining a high level of validity, uniqueness, and novelty. In the case studies, we demonstrate the application of PGMG to generate bioactive molecules in ligand-based and structure-based drug de novo design, as well as in lead optimization scenarios. Overall, the flexibility and effectiveness of PGMG make it a useful tool for accelerating the drug discovery process.