Hydrophobic modified cationic collagen flocculant P(C-AM-DAC-BA) was synthesized by graft copolymerization using gelatin which was extracted from leather wastes as raw materials, acrylamide (AM), acryloyl oxyethyl trimethyl ammonium chloride (DAC) and butyl acrylate (BA) as the monomer (AM: DAC: BA molar ratio is 80:18:2), meanwhile, the synthesis reaction was initiated with tert buty hydroperoxide and focal sulfite sodium. The influences of the molar ratio of gelatin and monomer, initiator dosage, grafting temperature and grafting time on flocculation effects to the oilfield simulated wastewater were investigated. The synthesis conditions of P(C-AM-DAC-BA) were optimized by response surface methodology, and the optimum conditions were as follows: the molar ratio of gelatin and monomer of 1:2.04, initiator dosage of 0.032mol/L, grafting temperature of 49.2℃, grafting time of 2.8h. Under these conditions, the turbidity removal rate was 91.5%.