Microcapsules of tilapia oil was prepared by using spray-drying method in this study. The microencapsulation rate was chosen as the evaluation index, six variables, such as the proportion of two kinds of starch, oil content, homogeneous times, homogeneous pressure, inlet-air temperature, and inlet feed rate were optimized. The differences of oxidation stabilities between fish oil microcapsules and refined fish oil (added vitamin E, sesamol and TBHQ, respectively) were studied. The results showed that the optimal technological conditions of microencapsulation of tilapia oil were obtained as follows: 2:3 (w/w) for the rate of octenyl succinic acid modified starch Mira CAP to the octenyl succinic acid modified starch Mira mist SE; 30% for the oil content; 3 times for the homogenization under 25 MPa of the homogenization pressure; 170 ℃ for the temperature of inlet-air and 10mL/min for the inlet feed rate, the microencapsulation efficiency of tilapia oil microcapsules reached up to 95.9%±0.73%. The sensory evaluation and physicochemical indexes (Moisture content: 1.93%, Surface oil content: 0.59%, POV: 2.10 mmol/kg) of microencapsulation products met the requirements of fish oil microcapsule standard of the aquatic product industry of China SC/T 3505-2006. By scanning electron microscope, the micro-structure observation of the microcapsules of Tilapia oil showed that they had smooth surface, no cracks. The results of the oxidative stability showed that the microcapsules of fish oil had the best oxidative stability. After storage at (65±1) ℃ for 12 days, the peroxide value of microcapsules of fish oil was only 5.22 mmol/kg, which was lower than the industrial standard (6 mmol/kg), and TBA was also significantly lower than the refined fish oil. It was estimated that this kind of product could keep good quality for more than 1 year at ambient temperature. Among the fish oils added different antioxidants, the fish oil with TBHQ showed the best oxidation stability, it can keep good quality for 8 months.