The largest bioconcentration step of most metals, including methylmercury (MeHg), in aquatic biota is from water to phytoplankton, but the extent to which dissolved organic matter (DOM) affects this process for MeHg largely remains unexplored in marine systems. This study investigated the influence of specific sulfur-containing organic compounds and naturally occurring DOM on the accumulation of MeHg in a marine diatom Thalassiosira pseudonana. Initial uptake rate constants and volume concentration factors (VCFs) of MeHg were calculated to evaluate MeHg enrichment in algal cells in the presence of a range of organic compound concentrations. At environmentally realistic and higher concentrations, the addition of glycine and methionine had no effect on algal MeHg uptake, but thiol-containing compounds such as cysteine and thioglycolic acid reduced MeHg accumulation in algal cells at high added concentrations (> 100 times higher than naturally occurring concentrations). However, environmentally realistic concentrations of glutathione, another thiol-containing compound as low as 10 nM, resulted in a decline of ~ 30% in VCFs, suggesting its possible importance in natural waters. Humic acid additions of 0.1 and 0.5 mg C/L also reduced MeHg VCFs by ~ 15% and ~ 25%, respectively. The bioaccumulation of MeHg for T. pseudonana in coastal waters with varying levels of dissolved organic carbon (DOC) was inversely correlated with bulk DOC concentrations. Generally, naturally occurring DOM, particularly certain thiol-containing compounds, can reduce MeHg uptake by phytoplankton.