OBJECTIVE:To investigate the therapeutic effect of the Jianpi Liqi Fang(健脾理气方,JPLQF)com-bined with transcatheter arterial chemoemboliza-tion(TACE)in patients with hepatocellular carcino-ma(HCC)and spleen deficiency syndrome(SDS)and identify a potentialindicator of efficacy.METHODS:Ninety-nine patients with HCC who were diagnosed with SDS,non-spleen deficiency syndrome(NSDS),or no syndrome(NS)were treat-ed with JPLQF combined with TACE for three peri-ods.Therapeutic efficacy was compared among the groups.Plasma proteins were screened using la-bel-free discovery analysis and verified via en-zyme-linked immunosorbent assay(ELISA).Further-more,receiver operating characteristic(ROC)curves were analyzed to evaluate therapeutic indicators.RESULTS:After treatment,the Karnofsky Perfor-mance Status was significantly improved in the SDS group and significantly better than that in the NS group.The Traditional Chinese Medicine(TCM)syn-drome scores were lower in the SDS group after treatment and lower than those in the NSDS group.However,alanine aminotransferase,carbohydrate antigen 19-9,alpha-fetoprotein,and carcinoembry-onic antigen levels and white blood cell and plate-let counts did not differ among the groups.Serum aspartate aminotransferase levels in the SDS group were significantly lower after treatment than be-fore treatment,and total bilirubin levels were signif-icantly lower in the SDS group than in the NSDS group.Label-free analysis identified 24 differential-ly expressed proteins(DEPs)between the SDS and NS groups,including 17 and 7 upregulated and downregulated proteins,respectively.Fibulin-5(FBLN5)displayed the largest difference in expres-sion between the groups.ELISA confirmed that FBLN5 levels were significantly lower in the NSDS and NS groups than in the SDS group.Following treatment with JPLQF and TACE,FBLN5 expression was upregulated only in the SDS group.Further-more,ROC curve analysis indicated that FBLN5 may serve as a potential indicator of the efficacy of JPLQF combined with TACE in patients with HCC and SDS.CONCLUSION:JPLQF combined with TACE im-proved quality of life,clinical TCM symptoms,and liver function in patients with HCC and SDS.FBLN5 expression was significantly altered by treatment with JPLQF and TACE in patients with HCC and SDS.