A novel macromolecule flocculant dithiocarboxyl amino-methylated polyacrylamide (DTAPAM), which can be used to remove heavy metal ions, was synthesized with polyacrylamide, formaldehyde, dimethylamine, carbon disulfide and sodium hydroxide. The removal of Cd(Ⅱ) in aqueous solution was investigated to determine the optimal preparation conditions for DTAPAM. The main influencing factors and central values of levels in the preparation process were confirmed by Plackett-Burman design and steepest ascent experiment. And then through central composite design (CCD) of response surface methodology (RSM), the preparation conditions of DTAPAM were optimized. The results showed that the regression of the quadratic polynomial model established with CCD was significant while the lack of fit was not significant. The multiple correlation coefficient (R²) was 0.9371, which demonstrated the model had good fitness. The optimum conditions for the preparation of DTAPAM were as follows:the concentration of PAM was 2.7%; the molar ratio of PAM, CS₂ and NaOH was 1:2:1.4; pre-reaction temperature was 23℃; pre-reaction time was 15min; main-reaction temperature was 40℃; and main-reaction time was 90min. Under the optimum conditions, the removal rate of Cd(Ⅱ) could reach 95.83%, which was close to the predicted value 94.08% of the model. The result proved that the model established by RSM was reasonable and feasible.