In order to solve the shortcomings of a single flocculant, the inorganic-organic hybrid flocculant SiO2-CTS-DMDACC was successfully prepared by grafting copolymerization of chitosan (CTS), dimethyl diallyl ammonium chloride (DMDACC), and silicon dioxide (SiO2). The performance of SiO2-CTS-DMDACC in treating papermaking wastewater was investigated, and the mechanism of the flocculation process was analyzed. The results showed that the crystallinity of chitosan was reduced due to the introduction of DMDACC and SiO2. The water solubility and thermal stability of SiO2-CTS-DMDACC with the rough porous structure were enhanced. The introduction of DMDACC enhanced the cationic properties of CTS-DMDACC compared with CTS. In addition, compared to CTS-DMDACC, the introduction of SiO2 increased the viscosity of SiO2-CTS-DMDACC. The experimental results showed that the treatment effect and the flocculation performance of SiO2-CTS-DMDACC with CTS:SiO2:DMDACC of 1:2:4 were the best and better than that of CTS at pH 7 for the treatment of papermaking wastewater. The removal rates of turbidity, COD, and NH4+-N were 99.43%, 82.92%, and 78.43%, respectively. The experimental results revealed that charge neutralization was the main mechanism of SiO2-CTS-DMDACC, and the adsorption bridging and net sweeping played supplementary roles in the treatment of papermaking wastewater.