The emergence of drug-resistant tuberculosis is still causing a public health crisis. In low-income countries such as the Democratic Republic of Congo, tuberculosis has not been eradicated and the emergence of the multidrug-resistant form is observed in some countries. The objective of this study was to determine the risk factors that contribute to the emergence of multidrug-resistant tuberculosis in the Nzanza Health Zone in the city of Matadi. This case-control analytical study was conducted over a period from January to March 2020. It concerned all lung tuberculosis patients with positive microscopy with confirmed resistance to rifampicin and isoniazid, between the period from January to December 2019 and who freely consented to participate in the study. Data were collected based on interviews with study participants using a structured questionnaire and based on data from the Central Office of the Nzanza Health Zone. The data were analyzed using EPI INFO 7 and Excel software. The Chi-2 test was used to compare the observed proportions and the strength of the associations between the variables was assessed using the odds ratios (OR) with the significance threshold (p ˂ 0.05). The results of this research found that two factors significantly put patients at risk of multidrug-resistant tuberculosis: lack of knowledge of multidrug-resistant tuberculosis OR (3.636) CI 1,342-9,855) (p= 0.011) and alcohol consumption OR (3.61) (CI [1.29 - 10.07]) (p = 0.012). Our study sufficiently demonstrates that multidrug-resistant tuberculosis still represents a major public health problem in some regions of the world and more particularly in the Nzanza Health Zone in the City of Matadi in the Democratic Republic of Congo. However, the emergence of multidrug-resistant tuberculosis could be prevented by implementing community-based awareness strategies.