The degree of substitution (DS) of charged groups for a polymer significantly impacts its adsorption behaviors onto the interface and ultimately affects its applications and performance. Herein, the adsorption behavior of quaternary celluloses (QCs) with different DS (0.23 and 0.51) on charged surfaces (particularly silica surface) was investigated by quartz crystal microbalance with dissipation monitoring technique. Thermodynamic parameters associated with the adsorption of QCs were assessed with the extended Van’t Hoff equation. The results showed that the QC samples with a lower DS could adsorb more onto the silica surface but with a softer conformation. The QC with a higher DS demonstrated a more negative ΔG°, a more negative ΔH°, a slightly lower positive ΔS°, and a less favorable ΔCp than the counterpart, confirming that DS of QCs had a substantial impact on its adsorption behavior and the associated thermodynamics.