Tuberculosis (TB), which is a highly infectious air-bone disease is a major health problem in the world. TB treatment interruption refers to missing of appointments therefore a patient will miss taking drugs. This increases disease morbidity, mortality and contributes significantly to the development of drug resistant TB which is expensive to treat. Data on factors influencing TB treatment interruption in Imenti south were unavailable. The study objectives were to determine the demographic, health services, cultural and patient factors that influence TB treatment interruption. This was a descriptive cross-sectional study. Data was obtained from 247 TB patients randomly selected from treatment registers and who had missed taking drugs during the treatment period. Ten key informant interviews were conducted on heath care workers working in TB clinics. A researcher-administered questionnaire was used to collect data from HCWs and TB treatment interrupters. Data collected was cleaned, coded and keyed into statistical package for social sciences (SPSS). Linear regression was applied to identify the relationship between variables. Results were presented using tables. Results showed that majority of TB treatment interrupters were male (71.6%). The age group 15-34 years had the highest number (50.2%) of participants. Majority (54.7%) had attained primary education. More than half (51%) were single and majority (95.1)% were Christians (Catholics and protestants). The source of income was largely farming (39.9%) and most had of less than 10000Kenya shillings (66.9%). Most were residing in rural areas (85.9%) and less than 5 kilometers (64.9%) from the health facility they attend. The demographic factors like age, marital status, level of education did not have any relationship with TB treatment interruption (p>0.05). Most respondents prefer Government health facilities (65.3%). The attitude of HCWs was mostly positive (96%) and drugs are mainly available (93.1%). TB patient mostly knew about TB before diagnosis (72.2%) and source of knowledge was varied but mostly from friends (40%). Relationship with their family mostly changed negatively after TB diagnosis (56%) and largest number interrupted because they forgot appointment dates (41.5%). A leading number of TB treatment interrupters are smokers (60.9%) and alcohol abusers (60.9%). The study concluded that: Majority of TB treatment interrupters are male and people in the reproductive age. Majority of the TB treatment interrupters are drug abusers and people of low economic status. The study recommended that: TB clinics in-charges should remind the TB patients about their appointment dates using mobile telephone short message. The health care workers should disseminate health messages on TB and drug abuse targeting the population with particular emphasis on males and those in the reproductive age group. Treatment supporters should also assist in provision of psychological and moral support of TB patients. Further research should be conducted on short term regimen of TB drugs to enhance adherence and improve treatment outcomes.