Two hundred and nine Yemeni with P. falciparum local strain satisfing all criteria of WHO for monitoring chloroquine sensitivity by in vivo and in vitro tests in urban and rural population of Al-Hodiedah G. were interviewed to study the human factors causing the persistence of chloroquine resistant. A pre-designed questionnaire sheet was used for every case, which included data concerning assessment of chloroquine resistant problem. The results revealed that, 54.7% of the studied group had used chloroquine for malaria treatment. About 75.0% were used antimalarial drugs by over the counter (OTC) i.e. self medication which was more common in rural (76.9%) than urban areas (63.6%). Chloroquine resistant was increased with the decrease of education level; decrease income/capita/month; among younger age-group (<15 years); and sleeping in open air in courts (56.3%, 57.8%, 56.6% and 66.7% respectively). The highest percentage of chloroquine resistant (71.0%) was recorded among cases with high parasite density (>1000 asexual parasite/microL); in presence of gametocytes (82.6%); among cases who did not complete antimalarial course (89.7%); those who gave a history of receiving antimalarial drugs without laboratory diagnosis (75.0%); those keeping leftover drugs after usage (63.8%) and reading expiry date and pamphlet of malaria drugs (26.9%). The results suggested the need for increasing of public awareness on emergence and spread of chloroquine-resistant and to outline potential risk factors useful for health workers in Yemen, especially in remote areas to identify high risk P. falciparum patients for chloroquine resistance before treatment.