Calcium carbonate (CaCO3) is a widely used inorganic powder, but its industrial applications are limited by its hydrophilicity and oleophobicity. Surface modification of CaCO3can improve its dispersion and stability in organic materials and further improve its potential value. In this study, CaCO3particles were modified with silane coupling agent (KH550) and titanate coupling agent (HY311) combined with ultrasonication. The oil absorption value (OAV), activation degree (AG), and sedimentation volume (SV) were employed to evaluate the modification performance. The results showed that the modification effect of HY311 on CaCO3was better than that of KH550, and ultrasonic treatment played an auxiliary role. Based on response surface analysis, the optimal modification conditions were determined as follows: the HY311 dosage was 0.7%, the KH550 dosage was 0.7%, and ultrasonic time was 10 min. The OAV, AG, and SV of modified CaCO3under these conditions were 16.65 g DOP/100 g, 99.27%, and 0.65 mL/g, respectively. The SEM, FTIR, XRD and thermal gravimetric analyses indicated successful coating of HY311 and KH550 coupling agents on the surface of CaCO3. The optimization of the dosages of two coupling agents and ultrasonic time improved the modification performance significantly.