OBJECTIVE：To explore t he risk factors that may lead to the ineff ectiveness of using palonosetron combined with dexamethasone to prevent chemotherapy-induced nausea and vomiting （CINV），and to provide a reference for the rational choice and use of antiemetic drugs. METHODS ：In a retrospective case-control study ，871 patients who used palonosetron combined with dexamethasone to prevent CINV in a tertiary cancer hospital from 2016 to 2020 were selected as the object. Totally 32 related data such as demographic data ，living habits ，medical history ，examination information and treatment information were counted as variables. Combined with single factor regression ，multi-factor regression， likelihood ratio forward or backward stepwise 163.com regression were used to comprehensively screen the factors for many times. The standard target factors screened by stepwise E-mail：kongtiandong@126.com regression were included in the multivariate Logistic regression analysis，and the regression model was evaluated by the ROC c urve. RESULTS ：The multivariate Logistic regression model fitted well（AUC in ROC was 0.83，but 0.82 after screening ）. The results showed that there were 15 statistically significant independent influential factors ，including 12 independent risk factors ，ie. poor nutritional status （OR＝2.11，95％CI（1.05，4.22），P＝0.036）， history of gastrointestinal disease （OR＝2.76，95％CI（1.87，4.07），P＜0.001），abnormal electrolyte level （OR＝2.54，95％CI （1.74，3.69），P＜0.001），nausea and vomiting 24 h before chemotherapy （OR＝8.47，95％CI（3.28，21.91），P＜0.001），history of chemotherapy-induced vomiting （OR＝3.20，95％ CI （2.18，4.71），P＜0.001），high risk level of vomiting caused by chemotherapy（OR＝3.16，95％CI（2.38，4.20），P＜0.001），application of opioid combined with non-steroidal analgesics （OR＝ 4.18，95％CI（2.06，8.49），P＜0.001），the use of other drugs that stimulate the intestine and stomach （OR＝2.49，95％CI（1.28， 4.83），P＝0.007），history of surgery （OR＝1.88，95％CI（1.34，2.63），P＜0.001），high level of albumin （OR＝1.05，95％CI （1.01，1.08），P＝0.015），multiple days of single chemotherapy （OR＝1.69，95％CI（1.11，2.56），P＝0.014），and opioid analgesia medicine （OR＝1.71，95％CI（1.15，2.53），P＝0.007）；and the following 3 independent protective factors included long time of diagnosis （OR＝0.65，95％CI（0.46，0.93），P＝0.019），non-first chemotherapy （OR＝0.52，95％CI（0.33，0.83），P＝ 0.006），and drugs combined chemotherapy （OR＝0.55，95％CI（0.34，0.90），P＝0.018）. CONCLUSIONS ：Patients with the following conditions are more likely to experience CINV prevention ineffectiveness ，ie. single long-term chemotherapy ，application of chemotherapy plan with a higher risk of emesis ，history of chemotherapy-induced vomiting ，history of gastrointestinal diseases ， nausea and vomiting 24 hours prior to chemotherapy ，history of surgery ，within 1 year of diagnosis ，chemotherapy for the first time，use of opioids ，use of 5-HT3 reuptake inhibitors ，malnutrition and electrolyte disorders.