Objective To systematically review the effectiveness and safety of implanting sustained-release 5-fluorouracil during hepatectomy in patients with primary liver cancer (PLC). Methods We electronically searched the following databases including CENTRAL, MEDLINE, EMbase, WanFang Data, CBM, CNKI and VIP to collect randomized controlled trials (RCTs) on the effectiveness and safety of implanting sustained-release 5-fluorouracil during hepatectomy vs. hepatectomy alone for PLC from inception to October, 2012. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results A total of 6 RCTs involving 951 patients were included. The results of meta-analysis showed that, implanting sustained-release 5-fluorouracil during hepatectomy significantly decreased the total recurrence rates of 1-year and 3-year (1 year: RR=0.48, 95%CI 0.36 to 0.65, Plt;0.000 01; 3 years: RR=0.69, 95%CI 0.50 to 0.96, P=0.03). However, the two groups were alike in decreasing the surem levels of AFP. Besides, the commonly-seen adverse reaction of implanting sustained-release 5-fluorouracil during hepatectomy included abdominal pain and bile leakage. Conclusion Implanting sustained-release 5-fluorouracil during hepatectomy can decrease the 1-year and 3-year recurrence rates of PLC patients, especially for HCC at the early stage. But this conclusion should be interpreted with caution and needs more strictly-designed RCTs with large sample size and enough long follow-up to verify.