BackgroundCOVID-19 pandemic affected common disease infections, while the impact on hand, foot, and mouth disease (HFMD) is unclear. Google Trends data is beneficial in approximately real-time statistics and easily accessed, expecting to be used for infection explanation from information-seeking behavior perspectives. We aimed to explain HFMD cases before and during COVID-19 using Google Trends data. MethodsHFMD cases were obtained from the National Institute of Infectious Disease, and Google search data from 2009 to 2021 was downloaded using Google Trends in Japan. Pearson correlation coefficients were calculated between HFMD cases and the search topic "HFMD" from 2009 to 2021. Japanese tweets containing "HFMD" were retrieved to select search terms for further analysis. Search terms were retained with counts larger than 1000 and belonging to ranges of infection sources, susceptible sites, susceptible populations, symptoms, treatment, preventive measures, and identified diseases. Cross-correlation analyses were conducted to detect lag changes between HFMD cases and HFMD search terms before and during COVID-19. Multiple linear regressions with backward elimination processing were used to identify the most significant terms for HFMD explanation. ResultsHFMD cases and Google search volume peaked around July in most years without 2020 and 2021. The search topic "HFMD" presented strong correlations with HFMD cases except in 2020 when COVID-19 outbroke. In addition, differences in lags for 73 (72.3%) search terms were negative, might indicating increasing public awareness of HFMD infections during the COVID-19 pandemic. Results of multiple linear regression demonstrated that significant search terms contained the same meanings but expanded informative search content during COVID-19. ConclusionsSignificant terms for HFMD cases explanation before and during COVID-19 were different. The awareness of HFMD infection in Japan may improve during the COVID-19 pandemic. Continuous monitoring is important to promote public health and prevent resurgence. Public interest reflected in information-seeking behavior can be helpful for public health surveillance.