3D-QSARs for the inhibition activities against protox by herbicidal 2-N-phenylisoindolin-1-one derivatives were studied quantitatively using CoMFA and CoMSIA methods. The result of the statistical quality of optimized CoMSIA model 2 ($FF:;{r^2}_{cv.};;0.973;&;{r^2}_{ncv.};;0.612$) was higher than that of CoMFA model 1 ($AF:;{r^2}_{cv.};;0.414;&;{r^2}_{ncv.};;0.909$). Also, the relative contribution of the optimized CoMSIA model 2 showed the steric (24.6%), electrostatic (31.0%), hydrophobic (ClogP, 23.4%) and H-bond acceptor field (21.0%), respectively. From the results of the contour maps, the protox inhibition activities are expected to increase when steric favor and H-bond acceptor favor groups are substituted on $R_2$ position and positive favor group are substituted on $C_2,;C_3,;and;C_5$ atom in phenyl ring of $R_2$ position. And the inhibition activities are expected to increase when hydrophobic favor group is substituted on $C_1,;C_3$ atom in phenyl ring of $R_2$ position and $C_1$ atom of $R_2$ position and hydrophilic favor groups are substituted on $C_4$ atom in phenyl ring of $R_1$ position and the terminal group of $R_1$ position.