Skimmed yak milk was selected for this research and the titratable acidity at 3.5h as the test indicator. Box-Behnken central composite experiment was designed based on optimal combination of fermentation starters to research the effect of Lactobacillus delbrueckii subsp bulgaricus(MGD1-3), Streptococcus thermophilus(MGB39-5), Streptococcus thermophilus(G81-1), and Lactobacillus plantarum(BM5152), which were screened from pastoral areas to the titratable acidity. The result showed that the optimal combination of fermentation starters was MGD1-3 3.06%, MGB39-5 0.64%, G81-1 0.55%, and BM5152 2.04% and the titratable acidity was 75.87°T. In order to facilitate the practical operation, the proportion of MGD1-3∶MGB39-5∶G81-1∶BM5152=30∶6∶5∶20 and 6.0% of inoculum size based on volume fraction were selected. Under these conditions, the average titratable acidity was 74.21°T of three parallel trials. Compared with the sensory and physical and chemical indicators of milk dried residue came from optimized combination of fermentation starters and pastoral areas, the result showed that the optimized combination of fermentation starters was reliable.