Abstract: Objective To explore a cost-effective, convenient, simple, and accurate method for estimating the population size of drug users. Methods Six prefectural cities located in eastern, middle, western, and northern parts of Guangdong Province were selected. Simplified multiplier method and capture-recapture method were used to estimate the population size of drug users. Multipliers were obtained using the interview among the drug users in the detoxification centers. Ratios of estimated size of drug users over registered drug users offered by local public security bureaus were calculated in each of cities. Results The estimated lowest and highest population sizes of drug users in the six cities by multiplier method were （4 883, 9 669）,（598, 676）,（3 360, 4 206）,（7 908, 16 920）,（1 375, 5 248）, and（657, 1 321）. The ratios of estimated population sizes to the number of the current registered drug users were (0.8, 1.5), (1.5, 1.7), (1.7, 2.1), (0.7, 1.4), (0.3, 1.3), and (1.5, 3.0), respectively. The corresponding sizes by capture-recapture method were （4 918, 5 048）,（1 259, 1 259）,（4 033, 4 735）,（9 921, 10 976）,（1 995, 2 134）,（1 355, 1 355） and the ratios were (0.8, 0.8), (3.1, 3.1), (2.0, 2.4), (0.8, 0.9), (0.5, 0.5),and (3.1, 3.1). Conclusion Compared with the capture-recapture method, the simplified multiplier method was feasible, rapid, and reliable, and can be used for the areas with limited resources to apply the ratios obtained in the study or used directly.