Objective To identify the risk factors related to malaria infection in those who traveled to Africa and returned to Shanglin County of Guangxi. Methods An epidemiological investigation and Plasmodium detection were done using a case-control study method in 2018. The cases with Plasmodium positive examined by microscopy or PCR test were grouped as case group, while those with negative results were grouped as a control group. The malaria infection risk factors were investigated by a questionnaire answered by those returned from a travel to Africa, with and without malaria infection. The questionnaire included general information, past medical history and anti-malaria treatment, working and living conditions when abroad, knowledge of malaria prevention and control and behavioral awareness related to malaria infection and so on. The collected information was analyzed to compare the difference of each factor between the case group and the control group. The potential risk factors related to malaria infection were analyzed using an unconditional multivariate logistic regression analysis method by setting the case group as the result variable and other factors as the explanation variable. Results Total 465 people returned from a travel to Africa were enrolled in the investigation related to the malaria infection in Africa, among them 149 were identified as Plasmodium infection positive and 316 as negative. Univariate analysis showed that there were significant differences for the five variables between the case group and the control group (P ≤ 0.05), including age (< 30: 17.5% and 7.6%, 30-39: 40.3% and 40.8%, 40-39: 24.2% and 32.6%, ≥ 50: 18.1% and 19.0%）, living ecological environment (forest: 41.6% and 43.4%, jungle: 41.6% and 26.3%, meadow: 5.4% and 3.5%, uncultivated: 10.7% and 22.8%, mixed: 0.7% and 4.1%), the cultivated crop type (rice: 95.3% and 89.9%, other: 4.7% and 10.1%), outdoor activities in the evening (yes: 56.4% and 62.0%, no: 43.6% and 38.0%), and outdoor activity spent time (no: 43.6% and 38.0%, 1-30 min: 8.1% and 17.4%, 31 min-1 h: 1.3% and 2.9%, 1-2 h: 0.7% and 1.6%, ≥ 2 h: 46.3% and 40.8%), respectively. Multivariate logistic regression analysis showed that the living environment in Africa for case group and control group was in city： 4.0%, 2.2%; in countryside: 7.4%, 3.5%; in the wild: 87.3%, 91.8%; and mixed： 1.3%, 2.5%, respectively, with OR = 1.8(1.0-2.8). The living house for case group contained less percentage of window and door screen (7.4%) than control group (12.0%) with OR = 0.2 (0.1-0.8). Conclusion The results conclude that people who lived in houses without door and window screens, went outdoors in the evening, and spent longer time outdoors had higher chance to get malaria and these activities are the important risk factors for malaria infection in Africa. Interestingly, people living in the city or integrated areas had the higher risk to get infected than those living in the field.