Most of the methods used for estimating the influenza vaccine effectiveness (IVE) target the individuals who have an influenza-like illness (ILI) rather than virologically-proven influenza and access the healthcare system. The objective of this study was to estimate the 2012–2013 IVE in general French population, using a cohort of volunteers registered on GrippeNet.fr, an online surveillance system for ILI. The IVE estimations were obtained through a logistic regression, and analyses were also performed by focusing on at-risk population of severe influenza, and by varying inclusion period and ILI definition. Overall, 1996 individuals were included in the analyses. The corrected IVE was estimated to 49% (20 to 67) for the overall population, and 32% (0 to 58) for the at-risk population. Three covariables appeared with a significant effect on the occurrence of at least one ILI during the epidemic: the age (P = 0.045), the presence of a child in the household (P < 10−3), and the frequency of cold/flu (P < 10−3). Comparable results were found at epidemic peak time in the hypothesis of real-time feed of data. In this study, we proposed a novel, follow-up, web-based method to reveal seasonal vaccine effectiveness, which enables analysis in a portion of the population that is not tracked by the health care system in most VE studies.