Objective. To compare the efficacy and safety of gemcitabine plus cisplatin (GP) and 5-fluorouracil plus cisplatin (PF) for metastatic nasopharyngeal carcinoma. Methods. The clinical trials of GP and PF in the treatment of metastatic nasopharyngeal carcinoma (NPC) were searched in PubMed, EMBASE, Cochrane Library, and Web of Science. The literature search met the inclusion and exclusion criteria. The software Revman 5.4 was used for data analysis, and STATA 15.0 was used for publication bias. Results. 10 studies were included in this meta-analysis. The results showed that the GP group had a higher clinical remission rate than the PF group (RR = 1.22, 95% CI (1.03–1.44),
P
=
0.02
,
P
=
0.02
). GP and PF groups in OS, PFS, and DMFS had the same effect at 1, 2, and 3 years (OS at 1 year: RR = 1.04, 95% CI (0.95–1.15),
P
=
0.37
,
P
=
0.37
; 2 years: RR = 1.08, 95% CI (0.94 1.23),
P
=
0.28
,
P
=
0.28
; 3 years: RR = 1.07, 95% CI (0.89 1.29),
P
=
0.46
; PFS at 1 year: RR = 1.98, 95% CI (0.29 13.44),
P
=
0.49
; 2 years: RR = 3.09, 95% CI (0.10 97.55),
P
=
0.52
; 3 years: RR = 0.95, 95% CI (0.73 1.24),
P
=
0.71
; DMFS at 1 year: RR = 1.01, 95% CI (0.90–1.14),
P
=
0.83
; 3 years: RR = 1.10, 95% CI (0.85–1.41),
P
=
0.47
. The number of hematological adverse reactions occurred in GP group was higher than the PF group. Conclusion. The GP and PF groups had similar OS, PFS, and DMFS, but the GP group had a higher clinical remission rate. Therefore, GP may be the first choice for metastatic NPC.
