Excess phosphorus (P) and nitrogen (N) is the fundamental driver of harmful cyanobacterial blooms (cyanoHABs), but other elements also influence algal abundance and composition. Silicon (Si) in particular plays a key role in phytoplankton dynamics due to varied Si requirements among major algal groups. Diatoms and a few other siliceous groups have a high Si demand, whereas cyanobacteria and chlorophytes have little or no direct Si requirement. The silicon (Si) depletion hypothesis, developed in the 1970s, posits that a long-term decline in dissolved Si (DSi) increases the susceptibility of freshwaters to cyanoHABs. The Ohio River is the second largest river in the U.S. and has experienced substantial cyanoHABs in recent years. Here I present an analysis of nearly 50 years of nutrient data in the context of Si:N:P stoichiometry, hydrological variability, and susceptibility to cyanoHABs in the Ohio River. Annually, DSi (as SiO2) ranged from >6 to <1.5 mg/L, with low concentrations usually occurring during June-August. This pattern was consistent throughout the period of record (1973-2021). In about 85% of samples, TN:TP molar ratios indicated P limitation. In 50% of samples, DSi:TP ratios indicated Si limitation of diatoms, consistent with research from the 1990s that reported Si limitation in the Ohio River. The Indicator of Freshwater Eutrophication Potential (IFEP) is a stoichiometric index that expresses P:Si imbalance as non-siliceous algal production, i.e., it indicates risk for cyanoHABs. The IFEP was strongly and directly related to discharge when using TP, but was inversely related to discharge when soluble reactive P was used in the index. This result suggests the bioavailability of particulate and dissolved organic P could be an important modifier of risk for cyanoHABs in rivers. From this analysis it appears that annual DSi depletion in the Ohio River could serve as a contributor to cyanoHAB formation.