The invention discloses a blast hole setting method and a blasting method for heavy-water mine shaft excavation. The blast hole setting method comprises the following steps: injecting slurry to a working face of sinking and driving engineering to prevent floods by water control, and cleaning all slurry-injecting holes to form cleaned slurry-injecting holes 3; (2) calculating number of peripheral holes 1 by utilizing a formula (I) according to a practical dimension value and slurry-injecting parameters of sinking and driving engineering; (3) uniformly arranging the peripheral holes 1 and the cleaned slurry-injecting holes 3 along an engineering outline 2; and (4) forming other working face blast holes according to excavation blasting. A free space is supplemented by utilizing cleaned slurry-injecting holes, and a vibration isolating zone is formed at the periphery of the engineering outline by virtue of blasting effect of the blast holes so as to isolate impact waves generated by follow-up blasting, so that surrounding rocks outside the engineering outline are effectively prevented from being damaged, cracks inside the surrounding rocks are prevented from being expanded and developed, formation of an underground water guide channel is avoided, and a water inrush accident of underground water is avoided; and number of the peripheral holes is effectively reduced, explosive load is reduced and engineering excavation cost is reduced.