A facile solvothermal-calcining route for the large-scale synthesis of uniform beta-Bi2O3 nanospheres has been demonstrated. The morphology, structure, and photoabsorption of beta-Bi2O3 were characterized, and the effects of the preparation conditions on the structural properties of products were analyzed. The results show that monodisperse bismuth nanospheres are formed through the solvothermal reaction where the D-fructose acting as the dominant reductant, and subsequently converted to beta-Bi2O3 nanospheres after the calcination in air. It is shown that the composition and structure of the products are greatly affected by the amount of D-fructose, the solvothermal and calcination temperature. The formation mechanism of beta-Bi2O3 nanospheres is assumed to undergo the "in situ reduction" of Bi(III)-ethylene glycol complex spheres which serve as self-sacrificing templates, followed by the "in situ oxidation" of bismuth nanospheres by oxygen during the calcination in air. The visible light-induced photocatalysis of the synthetic photocatalysts applied to the degradation of acetaminophen (APAP, a widely occurring human-derived pharmaceutical found in the environment) has been studied systematically. The photocatalytic reaction of APAP over the beta-Bi2O3 nanospheres follows pseudo first-order kinetics according to the Langmuir-Hinshelwood model, and exhibits a higher reaction rate constant, which is 2.5, 7, 8.1, and 79 times higher than that of commercial Bi2O3, synthetic alpha-Bi2O3, nitrogen doped TiO2 (N-TiO2), and Degussa P25, respectively. The superior photocatalytic activity is attributed to the narrower band gap energy (approximately 2.36 eV), nanostructure, good dispersion and high oxidation power of the beta-Bi2O3 nanospheres. Only one intermediate at m/z 110 can be detected by liquid chromatography/mass spectrometry (LC/MS) in the photodegradation process, while several low-molecular-weight organic acids were identified by ion chromatography (IC) analysis. By combining with the experimental determination of reactive oxygen species in the photocatalytic process and the theoretical calculation of frontier electron density of APAP, a simple, hole-predominated photodegradation pathway is proposed. In addition, the high mineralization efficiency indicates that the as-synthesized beta-Bi2O3 nanospheres photocatalyst can avoid secondary pollution during photocatalysis, which is important in practical applications. (C) 2013 Elsevier B.V. All rights reserved.