In our study, the tear proteome was compared with identify possible mechanisms and biomarkers for predicting acupuncture effectiveness in VDT-related dry eye. The results showed that the Ocular Surface Disease Index (OSDI) scores were significantly different between the acupuncture group (AC group) and artificial tears group (AT group) at the end of the study, whereas the Tear film break-up time (TFBUT) and Schirmer I test (SIT)were not significantly different between the groups. Proteome changes pre- and post-treatment in the AC group were associated with B cell-related immune processes, inflammation, glycolysis, and actin cytoskeleton.