Tumor lysis syndrome (TLS) is a cancer chemotherapy-associated oncologic emergency. Although there have recently been substantial developments in cancer chemotherapy, these may increase the risk of TLS. In this study, we aimed to identify anticancer agents that increase TLS risk, as classified by a TLS panel consensus, using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. TLS reports were retrieved from the FAERS database, and reporting odds ratios (RORs) were used to estimate associations between TLS and old and new anticancer agents or their combinations. We identified 1615 TLS cases among 4 330 807 case reports covering the period from the first quarter of 2004 through to the first quarter of 2014. Using RORs, we detected significant risk signals for 56 of 64 anticancer agents (37 and 19 cytotoxic and molecular-targeted drugs, respectively). Bortezomib in particular was found to be associated with a high ROR and numerous TLS events relative to those of other molecular-targeted drugs (161 TLS events, ROR = 28.89, 95% confidence interval: 24.53-34.02). The main indication of bortezomib is multiple myeloma, a low-risk disease for TLS occurrence. We conducted a detailed analysis focusing on regimens containing bortezomib, lenalidomide, and thalidomide. Bortezomib-containing treatment regimens were more frequently associated with TLS events than were other multiple myeloma treatment regimens (cytotoxic chemotherapy, lenalidomide, and thalidomide). Although the risk of TLS in patients with multiple myeloma is generally considered low, a cautious evaluation of TLS risk is recommended for patients receiving bortezomib-containing therapy.