As a new field of seeker development, the phased array radar seeker has the advantages of small size, light weight, high power and high reliability. Since the pattern of phased array antenna changes direction in space from the mechanical platform to the discrete digital control system, the antenna pointing error is produced; at the same time, there is radome boresight error. Affected by these two errors, the pointing error of phased array radar seeker is more serious, which will cause the parasitic coupling problem of the guidance system and affect the stability of the guidance system. In this paper, by constructing the guidance system model of phased array radar seeker, the influence mechanism of seeker pointing error is analyzed, and an on-line estimation and compensation method of seeker pointing error slope is proposed by combining multiple-model with extended Kalman filter. Finally, digital simulation is carried out. The simulation results show that the method proposed can effectively estimate the seeker pointing error slope, the stability and accuracy of the guidance system can be improved with pointing error slope compensation.