Silicon wafer thinning process is meeting great challenges to fulfill requirements of ultra-thin IGBT for automotive applications. Chemo-mechanical grinding (CMG) process is potentially emerging stress relief thinning process which combines the advantages of fixed abrasive machining and chemical mechanical polishing (CMP). A major issue in CMG of Si wafers is the relatively low material removal rate (MRR). This paper studies the influence of the wheel specifications and grinding conditions on the MRR of CMG. Two sets of three-factor two-level full factorial designs of experiment (DOE) are employed to reveal the main effects and interacted effects of CMG wheel specifications and grinding parameters on MRR. The optimal combination scenarios for improving MRR of CMG are analysized and obtained. By use of the optimal CMG wheel and grinding parameters, the MRR of more than 60nm/min is achieved.