Delivering safe and effective therapeutic treatment to patients is one of the grand challenges in modern medicine. However, drug safety research has been progressing slowly in recent years, compared to other fields such as biotechnologies and precision medicine, due to the mechanistic complexity of adverse drug reactions (ADRs). To fill up this gap, we develop a new database, the Adverse Drug Reaction Classification System-Target Profile (ADReCS-Target, http://bioinf.xmu.edu.cn/ADReCS-Target), which provides comprehensive information about ADRs caused by drug interaction with protein, gene and genetic variation. In total, ADReCS-Target includes 66,573 pairwise relations, among which 1710 are protein-ADR associations, 2613 are genetic variation-ADR associations, and 63,298 are gene-ADR associations. In a case study of exploring the mechanism of rash, we find that HLAs, C1QA and APOA1 are the key gene players and thus can be potential targets (or biomarkers) in monitoring or countermining rashes. In summary, ADReCS-Target can be a useful resource for the biomedical scientific community by serving researchers in the fields of drug development, clinical pharmacology, precision medicine, and from web lab to high-throughput computational platform. Particularly, it helps to identify drug with better ADR profile and design safer drug therapy regimen.