Objective To observe the clinical efficacy and safety of nedaplatin combined with paclitaxel liposome on advanced esophageal cancer. Methods 80 advanced esophageal cancer patients were divided randomly into two groups, including study group treated with nedaplatin and paclitaxel liposome and control group of chemotherapy with nedaplatin and paclitaxel regimen with 3-week as a course of treatment. The clinical efficacy, quality of life and adverse reaction were compared between both groups after 2 courses of treatment. Results After two courses of treatment, the effective rates in study group and control group were 57.5% (23/40) and 55.0% (22/40), respectively, and there was no significant difference (χ2=0.704, P>0.05). The quality of life score before the treatment had no significant difference between the two groups (t=0.794, P>0.05). After one course of treatment, the quality of life was improved more than that in control group (t=5.782, P 0.05), but the incidences of nausea and vomiting, dyspnea, liver function, renal function damage in study group were significantly lower than those in control group, and the differences were statistically significant (P<0.05). Conclusions Besides a favorable function in retention paclitaxel original medicinal mechanism, efficacy and indications, paclitaxel liposome can effectively avoid the risk of adverse events. Furthermore, paclitaxel liposome combined with nedaplatin for advanced esophageal cancer is worthy of wide application, due to the better curative effect and safety. Key words: Esophageal neoplasms; Nedaplatin; Paclitaxel liposome; Safety