<b><i>Background:</i></b> Dry eye disease (DED) has a higher incidence in old age and is seen predominantly in females worldwide. Neurosensory abnormalities, ocular surface inflammation and damage, film instability, and hyperosmolarity are major and proven pathologies responsible for a poor quality of life. Tear breakup time and Schirmer’s I test are predominantly used for the evaluation of primary outcomes in patients undergoing conventional treatment. A previous meta-analysis of some relevant studies proved that combination of acupoints could be more effective than single acupoint treatment. <b><i>Objectives:</i></b> The present study aimed to undertake association rule mining and examined the potential kernel acupoint combination in DED treatment constructed from the extracted randomized controlled trials (RCTs) based on a previous meta-analysis. <b><i>Methods:</i></b> We summarized 32 acupoints as binary data from the 12 eligible RCTs and analyzed them based on the Apriori algorithm. <b><i>Results:</i></b> TE23, BL2, ST2, ST1, EX-HN5, BL1, LI4, ST36, SP6, and KI3 were the 10 most frequently selected acupoints. The major associated rules in combination of acupoints were {TE23, LI4} ≥ {ST1} and {TE23, ST1} ≥ {LI4}, as inferred from 23 association rules. <b><i>Conclusions:</i></b> For acupuncture treatment of DED, combined TE23, LI4, and ST1 acupoints could be settled as the kernel of acupoint combination.