The aim of this study is to establish a method for determination of related substances in pholcodine crude materials. The contents of morphine, codeine, other unknown impurities and total impurities were determined by HPLC; the content of N-(β-chloroethyl) morpholine hydrochloride was determined by GC. The linear range was 0.4046-2.0232μg/mL for morphine (r=0.9994), 0.8122-4.0608μg/mL for codeine (r=0.9991) and 0.0101-0.1009 mg/mL for N-(β-chloroethyl) morpholine hydrochloride (r=0.9997). Average recoveries were 99.6% (RSD=4.57%), 103.67% (RSD=2.45%) and 101.3% (RSD=2.36%), resp. The limits of quantitation were 0.2, 0.4 and 5.0μg/mL. The method is selective, sensitive and accurate, and it can be used for determination of related substances in pholcodine crude materials.