Objective To evaluate the efficacy, safety and economical values of nucleic acid/nueleotides for clinical nutritional support and immune treatment. Methods The following electronic databases were searched: Chinese Biomedicine database (CBM), MEDLINE, EMBASE and SCI. Data were extracted by two reviewers. Applied RevMan 4.1 for statistical analyse. Results Forty-six randomized controlled trials were identified, involving nucleic acids/nucleotides for clinical nutritional support, infant feed, immune treatment. Eighteen randomized trials comparing the use of immunonutrition which comprises nucleotides with standard enteral nutrition in surgical and critical ill patients. Combined analysis directed that immunonutrition therapy decrease infection events, length of hospitalization and the cost. Only one trial reported the effects of adding nucleotides to breast milk substitute, but there is no valuable results for clinical practice. Twenty-seven low quality trials compared the use of "immune RNA (iRNA)" with standard methods in hepatitis, carcinoma and burn patients, combined analysis directed that there are not valid evidences to confirm the value of iRNA. Conclusions Immunonutrition may decrease infection rates, length of hospitalisation and cost in surgery and critical ill patients, but we can not affirm the role of the nucleotides in irmnunonutrition. No evidences support the point of adding nucteotides in breast milk substitute. Also, we can not affirm the role of iRNA in clinical immune regulation treatment. There are no available evidences in nucleic acids for caducity prevention and improvement of aging people’s health. Consequently, we advice Chinese health officials to enhance the management for applying "nucleic acids nutrients".