Butanetetracarboxylic acid (BTCA)/NaYF₄:Yb³⁺, Er³⁺ upconversion phosphors have been successfully synthesized by a one-step hydrothermal method. The SEM and XRD results show the as-prepared phosphors exhibit main hexagonal lattice structures and uniform morphologies. FT-IR spectra confirm that the surface of as-prepared phosphors is inherently modified with the carboxyl groups. Under the excitation of 980 nm, it has been observed that BTCA/NaYF₄:Yb³⁺, Er³⁺ upconversion phosphors have a higher upconversion luminescence efficiency than that coated with citrate, ethylenediamine tetraacetic acid (EDTA), or polyacrylic acid (PAA). These results indicate that the BTCA/NaYF₄:Yb³⁺, Er³⁺ phosphors may have superior optical properties, and thus have great potential for biological applications.