Purpose:　Anlotinib　is　widely　used　in　the　treatment　of　lung　cancer.　However,　there　remains　a　lack　of　predictive　biomarkers　to　effectively　gauge　the　response　to　anlotinib　therapy.　We　conducted　a　retrospective　study　to　preliminarily　explore　potential　risk　factors　that　might　predict　outcomes　in　lung　cancer　patients　undergoing　anlotinib　treatment.　Patients　and　Methods:　We　retrospectively　analyzed　lung　cancer　patients　treated　with　anlotinib　at　our　hospital　between　1　June　2018　and　1　June　2021.　Data　were　gathered　from　electronic　medical　records.　Demographic　and　clinical　characteristics　of　patients,　progression-free　survival　(PFS),　and　overall　survival　(OS)　were　described.　Predictive　factors　related　to　treatment　efficacy　were　preliminarily　analyzed　using　Cox　regression　and　Kaplan–Meier　survival　analyses.　Results:　After　adjusting　for　potential　confounders,　clinical　stage　IV　(hazard　ratio　[HR]　=　2.52,　95%　confidence　interval　[CI],　1.09–5.82,　p　=　0.0311),　N-terminal　fragment　brain　natriuretic　peptides　(NT-pro-BNP)　＞　300　pg/mL　(HR　=　2.54,　95%　CI,　1.17–5.52,　p　=　0.0183),　and　neuron-specific　enolase　(NSE)　＞　16.3　ng/mL　(HR　=　1.70,　95%　CI,　1.03–2.81,　p　=　0.0389)　were　associated　with　shorter　OS,　whereas　age　(HR　=　0.96,　95%　CI,　0.94–0.99,　p　=　0.0055)　was　associated　with　a　longer　PFS　in　fully　adjusted　model.　Kaplan–Meier　analyses　of　cumulative　risk　factors　(clinical　stage　IV,　NT-pro-BNP　＞　300　pg/mL,　and　NSE　＞　16.3　ng/mL)　indicated　that　patients　with　a　greater　number　of　coexisting　risk　factors　had　significantly　shorter　OS　(p　＜　0.0001).　Conclusion:　Clinical　stage　IV,　NT-pro-BNP　level,　and　NSE　level　were　identified　as　independent　prognostic　factors　for　lung　cancer　patients　undergoing　anlotinib　treatment.　Patients　with　multiple　high-risk　factors　may　derive　limited　benefit　from　anlotinib.　©　2025　The　Author(s).　The　Clinical　Respiratory　Journal　published　by　John　Wiley　&　Sons　Ltd.