Aiming at the gain, offset and time delay channel mismatches estimation problem of time interleaved ADC system, a high accuracy comprehensive approach based on least square was presented, which required no extra circuits and eliminated the limitation of channel number. Then Monte Carlo simulations were done to compare this approach with Cramer-Rao Lower Bound(CRLB). Finally, the estimation method was used to measure the channel mismatches of a real time interleaved 400 MSps/12 bit digitizer. Simulation and experiment demonstrated that the accuracy of the calculation method is high, and quantization error, spurious and harmonic distortion have little influence on it. This method can effectively obtain the channel mismatches of actual time interleaved ADC system.