Objective To investigate the effect of gemcitabine, paclitaxel combined with nedaplatin in treatment of locally advanced nasopharyngeal carcinoma. Methods 40 patients diagnosed as locally advanced nasopharyngeal carcinoma from May 2012 to August 2014 were randomly divided into observation group and control group. Patients in the observation group received gemcitabine plus nedaplatin chemotherapy, while those in the control group received paclitaxel plus nedaplatin chemotherapy. Then chemotherapy effect, adverse reactions, survival time and tumor marker contents were compared. Results The effective rate of the observation group was 65 % (13/20), which was higher than that (30 %, 6/20) of the control group (χ2 = 4.912, P< 0.05), however, there were no statistically differences in gastrointestinal reactions, bone marrow suppression, liver damage, kidney damage between groups (P> 0.05). Before chemotherapy, the SCCAg and CYFRA21-1 content of the control group were (2.30 ±0.31) ng/L and (18.27±2.19)μg/L, and the observation group were (2.34±0.27) ng/L and (18.48±2.25)μg/L, and there was no significant difference between the groups (P>0.05). After chemotherapy, the SCCAg and CYFRA21-1 content of the control group were (1.92±0.22) ng/L and (13.72±1.74) μg/L, and the observation group were (1.20 ±0.15) ng/L and (8.49 ±0.91) μg/L (P= 0.000). Conclusion Gemcitabine combined with nedaplatin chemotherapy can improve the chemotherapy effect and reduce tumor marker content, without increasing more adverse reactions, which is an ideal chemotherapy regimen for advanced nasopharyngeal carcinoma.