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Objective: To evaluate the effect of simple acupressure protocol in LIV3, LI4 and placebo points on the quality of life (QOL) in women with premenstrual syndrome (PMS)., Method: This paper reports a randomized, single blinded clinical trial. 97 participants (students in of Hormozgan University of Medical Sciences, Iran) with PMS were allocated to three groups to receive 20min acupressure on different acupoints for 14days before menstruation for three consecutive menstrual cycles (training and then two cycles self applied acupressure). The acupoints were LIV3 and LI4; one group received acupressure at a placebo point. Each participant completed the PSST scale (to determine PMS severity), HADS scale (for depression and anxiety), and quality of life SF12., Results: The number of people with moderate/severe PMS decreased in LIV3 and LI4 acupressure groups by the second and third cycles compared with the placebo group (p<0.04). Moreover, depression and anxiety scores significantly decreased in the LIV3 and LI4 groups by the second and third cycles compared with the placebo group (p<0.05).Analyzing the score of SF12 fields in the second and third cycles showed a significant difference in all dimensions between the intervention and placebo groups. There was no significant difference between LIV3 and LI4 acupressure groups in decrease of PMS symptoms, anxiety and depression and improving SF12scores (p<0.05)., Conclusion: Performing the simple acupressure protocol at LIV3 and LI4 is an effective method to decrease the severity of PMS symptoms, anxiety and depression, and to improve the QOL. Pressure at LIV3 and LI4 appears to be equally effective., (Copyright © 2017 Elsevier Ltd. All rights reserved.)