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A novel CuS grafted PEDOT:PSS conducting paper-based electrochemical immunosensor has been successfully fabricated for the detection of EpCAM antigen. Electrical conductivity is further improved by doping the CuS@PEDOT:PSS/WP electrode with different organic solvents such as N,N-dimethyl formamide (DMF), N,N-dimethyl acetamide (DMA), ethylene glycol (EG) and dimetyl sulfoxide (DMSO). It is observed that DMSO doped conducting paper shows the highest conductivity (6.1 × 10−2 S/cm) among all these solvents. This low cost, biodegradable electrochemical paper-based immunosensor (BSA/anti-EpCAM/EP) possesses a broad linear range from 0.01 pg/mL to 1000 ng/mL for EpCAM antigen detection. The immunosensor is found to have high sensitivity of 104.31 μA pg−1 mL. This conducting paper based immunosensor is further used to detect EpCAM antigen in human serum samples, thereby confirming a cost effective clinical tool over other costly conventional techniques. • An electrochemical paper-based immunosensor has been designed using CuS and PEDOT:PSS. • This low cost and flexible platform may be a promising candidate over other costly conventional electrodes. • It exhibits high sensitivity of 104.31 μA pg−1 mL in broad range of 0.01 pg/mL to 1000 ng/mL, for EpCAM detection. • The clinical applicability and validity has been checked with human serum sample. [ABSTRACT FROM AUTHOR]