AimsTo　investigate　the　predictive　value　of　baseline　C-reactive　protein　(CRP)　levels　on　the　efficacy　of　chemotherapy　plus　immune　checkpoint　inhibitors　(ICI)　in　patients　with　advanced　lung　squamous　cell　carcinoma　(LSCC).Materials　and　methodsIn　this　retrospective　multicenter　study　spanning　from　January　2016　to　December　2020,　advanced　LSCC　patients　initially　treated　with　chemotherapy　or　a　combination　of　chemotherapy　and　ICI　were　categorized　into　normal　and　elevated　CRP　subgroups.　The　relationship　between　CRP　levels　and　treatment　outcomes　was　analyzed　using　multivariate　Cox　proportional　hazards　models　and　multivariate　logistic　regression,　focusing　primarily　on　the　progression-free　survival　(PFS)　endpoint,　and　secondarily　on　overall　survival　(OS)　and　objective　response　rate　(ORR)　endpoints.　Survival　curves　were　generated　using　the　Kaplan-Meier　method,　with　the　log-rank　test　used　for　comparison　between　groups.ResultsOf　the　245　patients　evaluated,　the　105　who　received　a　combination　of　chemotherapy　and　ICI　with　elevated　baseline　CRP　levels　exhibited　a　significant　reduction　in　PFS　(median　6.5　months　vs.　11.8　months,　HR,　1.78;　95%　CI:　1.12-2.81;　p　=　0.013)　compared　to　those　with　normal　CRP　levels.　Elevated　CRP　was　identified　as　an　independent　risk　factor　for　poor　PFS　through　multivariate-adjusted　analysis.　However,　among　the　140　patients　receiving　chemotherapy　alone,　baseline　CRP　levels　did　not　significantly　influence　PFS.　Furthermore,　within　the　combination　therapy　group,　there　was　a　notable　decrease　in　the　ORR　(51%　vs.　71%,　p　=　0.035),　coupled　with　a　significantly　shorter　OS　(median　20.9　months　vs.　31.5　months,　HR,　2.24;　95%　CI:　1.13-4.44;　p　=　0.033).ConclusionIn　patients　with　advanced　LSCC,　elevated　baseline　CRP　levels　were　identified　as　an　independent　predictive　factor　for　the　efficacy　of　combination　therapy　with　chemotherapy　and　ICI,　but　not　in　chemotherapy　alone.　This　suggests　that　CRP　may　be　a　valuable　biomarker　for　guiding　treatment　strategies.