Modified Na-montmorillonite was prepared with cetyl trimethyl ammonium bromide (CTAB) as modifier. The effect of deionized water amount, CTAB amount, stirring speed, mixing temperature and drop in time on modified Na-montmorillonite interlamellar spacing was studied by uniform design and multivariate nonlinear regression. Composition, structure and microstructure of modified Na-montmorillonite were characterized. The results showed that compatibility of modified Na-montmorillonite increased, interlamellar spacing increased significantly. Primary and secondary sequence of factors on modified Na-montmorillonite interlamellar spacing is CTAB amount>mixing temperature>stirring speed>deionized water amount>drop in time. The optimization pconditions of modified Na-montmorillonite is deionized water amount 358 g, CTAB amount 0.47 g, stirring speed 2853 r/min, mixing temperature 75.6℃ and drop in time 128 min.