To explore the efficacy and safety of gemcitabine (GEM) combined with cisplatin (DDP) in the treatment of recurrent/metastatic nasopharyngeal carcinoma (NPC). A total of 100 patients with recurrent/metastatic NPC treated in the First Affiliated Hospital, Hengyang Medical School, University of South China from January 2018 to March 2020 were retrospectively enrolled. Based on different chemotherapy schemes, they were assigned to an observation (Obs) group (DDP + GEM, n = 55) and a control (Con) group [DDP + FU (fluorouracil), n = 45]. The two groups were compared regarding the following items: therapeutic efficacy; serum levels of platelet-derived growth factor-BB (PDGF-BB), soluble epithelial cadherin (SE-CAD), and inflammation-related factors before and after treatment; toxic and side effects; 1-year survival rate; and quality of life (QOL) 6 months after treatment. The Obs group outperformed the Con group in therapeutic efficacy (P < 0.05). There were no significant differences in the levels of PDGF-BB, SE-CAD, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α between the two groups before treatment (P > 0.05). After treatment, better improvements in PDGF-BB, SE-CAD and inflammatory factors were observed in the Obs group (P < 0.05). The toxic and side effects were significantly lower and the 1-year survival rate and patients' QOL after 6 months of treatment were significantly higher in the Obs group compared with the Con group (P < 0.05). GEM combined with DDP can provide more clinical benefits for patients with recurrent/metastatic advanced NPC, with less side effects, high tolerance and significant efficacy, which can be further promoted in clinical use.