Interaction between 8alkyl coptisine derivatives and lysozyme were investigated by measuring the quenching constants under different temperatures and analyzing the thermodynamic parameter. The result revealed that there was a strong fluorescence quenching effect of coptisine analogues on lysozyme. The data indicated both dynamic and static quenchings were involved in the quenching process. The thermodynamic parameters indicated that the interactions of coptisine analogues with lysozyme were driven mainly by hydrophobic force. UV absorption of lysozyme was more negatively affected by a longer alkyl chain. Compared to CopC86 and CopC84, CopC88 had the highest binding constant which is 2.063×107.