Numerous recent studies have reported that informal social contact with family and relatives generally improves happiness. However, several studies suggest that the effect of informal social contact with family and relatives might vary among countries. Therefore, by focusing on defamilialization, this article examines how the influence of informal social contact with family and relatives on happiness differs among less- and more-defamilialized countries. This article uses individual data from the 2007 International Social Survey Programme (ISSP) combined with country-level data and a country fixed-effects model with robust standard errors to examine the cross-level interaction effects of defamilialization and informal social contact with family and relatives on happiness. In a cross-national comparison, a moderation effect of defamilialization on the association between informal social contact with family and relatives and happiness was observed in the overall sample and in women. These results indicate that defamilialization might change the meaning of relationships with family and relatives.