Background: Standard precautions (SPs) including hand hygiene are considered fundamental protective measures to manage health care-associated infections (HCAIs) and to reduce occupational health hazards. The purpose of this research was to examine the effectiveness of an infection control link nurse (ICLN) program on compliance with SPs and hand hygiene among nurses. Methods: A quasi-experimental study with a pretest-post-test design was conducted with participating of 154 clinical nurses who worked in different wards of a tertiary referral teaching hospital in Iran. The intervention group (n = 77) had 16 infection control link nurses nominated. The control group (n = 77) received only the standard multimodal approach used in the hospital. Pre- and post-test assessment of compliance with standard precautions and hand hygiene compliance was performed via the Compliance with Standard Precautions Scale (CSPS) and the World Health Organization observational hand hygiene form. Two independent sample t-tests were used to examine differences between Compliance with Standard Precautions and hand hygiene Compliance among nurses in intervention and control group. Multiple linear regression analysis was used to assess the effect size. Results: After developing and implementing the infection control link nurse program, no statistically significant improvement was found in the Compliance with Standard Precautions (β = 5.18; 95% CI= -0.3-10.65, p = 0.064). An improvement in hand hygiene compliance was observed among nurses in the intervention group that improved statistically significant from 18.80% before the program to 37.32% 6 months after the program (β = 20.82; 95% CI 16.40-25.25, p < 0.001). Conclusions: Given the continuing level of interest that exists in improving health care workers' hand hygiene practices, the findings of this study provide significant practical implications for hospitals seeking to improve compliance with hand hygiene among nurses, showing the effectiveness of using infection control link nurse program. Further research is needed to assess effectiveness of using infection control link nurse program to improve compliance with standard precautions.