The cellulose powder was converted to carboxymethylcellulose (CMC) by etherification process using sodium monochloroacetate and sodium hydroxide. There are two reaction occur simultaneously during carboxymethylation that are the primary reaction which produces pure CMC and side reaction that produces undesired sodium glycolate. The carboxymethylation reaction was optimized against the reaction temperature, reaction time, SMCA concentration, NaOH concentration and the ratio solvent of ethanol:isopropanol. The Degree of Substitution (DS), viscosity and yield were analyzed with respect to the reaction conditions using response surface methodology. The method of analyzing the degree of substitution of CMC is back titration method. The produced CMC was identified by using Fourier Transform Infrared spectra (FTIR). The maximum DS obtained is 0.94, maximum yield is 22.0730 g and maximum viscosity 15.2 cP. After optimization of reaction conditions is carried out, the optimized DS obtained is 0.9424 and the optimized viscosity is 10.1 cP with yield is 22.1024 g.