Many cellular processes, such as the diffusion of biomacromolecules, the movement of molecular motors, and the conformational dynamics of proteins, are subjected to hydrodynamic forces because of the high viscosities of cellular environments. However, it is still unknown how hydrodynamic forces are related to the physical properties of different viscogens. Here, using the atomic force microscope-based force spectroscopy technique, we directly measured the hydrodynamic forces acting on a moving cantilever in various viscogen solutions. We found that the hydrodynamic force is not only dependent on the viscosity but also related to the molecular weight of viscogens. Counterintuitively, at the same macroscopic viscosity, the hydrodynamic force rises with the increasing molecular weight of viscogens, although the local microscopic viscosity of the solution decreases. This finding provides insights into the origin of hydrodynamic forces in biomolecule solutions and could inspire many force-spectroscopy-based techniques to measure the molecular weight and conformational changes of biomacromolecules in biological settings directly.