Objectives:　Anlotinib　is　a　novel　multi-target　tyrosine　Kinase　inhibitor　that　inhibits　VEGFR2/3,　FGFR1-4,　PDGFD　alpha/beta,　c-Kit　and　Ret.　In　the　phase　III　ALTER-0303　trial　(Clinical　Trial　Registry　ID:　NCT　02388919),　anlotinib　significantly　improved　overall　survival　versus　placebo　in　advanced　non-small-cell　lung　cancer　(NSCLC)　patients　who　had　received　at　least　two　previous　chemotherapy　and　epidermal　growth　factor　receptor/anaplastic　lymphoma　kinase　targeted　therapy　regimens.　This　study　assessed　quality　of　life　(QoL)　in　these　patients.　Methods:　Patients　were　randomized　(2:1)　to　anlotinib　or　placebo　up　to　progression　or　intolerable　toxicity.　The　QoL　were　assessed　using　the　European　Organization　for　Research　and　Treatment　of　Cancer　(EORTC)　Quality　of　Life　Questionnaire　Core　30　(QLQ-C30)　and　the　associated　EORTC　Quality　of　Life　Lung　Cancer　Specific　Module　(QLQ-LC13)　at　baseline,　end　of　cycle　1,　end　of　every　two　cycles,　and　at　the　final　visit.　The　analyses　were　conducted　in　the　first　6　cycles.　Differences　in　scores　of　10　points　or　more　between　two　arms　or　from　baseline　were　considered　clinically　meaningful.　Results:　A　total　of　437　patients　were　assigned　to　anlotinib　(n　=　294)　and　placebo　(n　=　143).　The　completion　rates　of　the　QoL　questionnaires　were　from　69.9%　to　97.0%.　Mean　scores　of　QLQ-C30　and　QLQ-LC13　subscales　were　similar　in　the　anlotinib　and　placebo　arms　at　baseline.　Compared　to　placebo,　anlotinib　improved　role　functioning,　social　functioning,　dyspnea,　insomnia,　constipation　and　financial　problems.　Only　sore　mouth　or　tongue　symptom　was　worse　in　the　anlotinib　arm　than　in　the　placebo　arm.　Conclusions:　Anlotinib　improved　quality　of　life　versus　placebo　in　advanced　NSCLC　patients　who　had　received　at　least　two　previous　chemotherapies.　The　QoL　analyses　provided　evidence　that　anlotinib　should　be　a　choice　for　the　third-line　treatment　or　beyond　in　advanced　NSCLC.