Loneliness is a growing public health problem that threatens physical and mental health to a large extent. Compelling evidence has shown that premature parental death is strongly associated with many mental health disorders in adulthood, but whether it increases the risk of loneliness remains unclear. In this large community-based study, we included 32,682 adult participants (20–93 years old) from Southwest China and used the three-item short version of University of California, Los Angeles, Loneliness Scale to identify participants with loneliness. A total of 1,975 participants reported loneliness, which resulted in a loneliness prevalence of 6.0% in Southwest China. Logistic regression was used to evaluate the association between early parental death and loneliness after adjusting for age, gender, education level, marital status, smoking and drinking status, living status, and chronic diseases. We found that early parental death was significantly associated with loneliness [odds ratio (OR) = 1.21, 95% confidence interval (CI), 1.03–1.42]. A Sensitivity analysis excluding those with mental health disorders (796 participants) yielded similar results (OR = 1.26, 95% CI = 1.06–1.49). We also found that being younger, single, divorced, or widowed, and more educated; living alone; and having chronic disorders were associated with loneliness. We conclude that childhood parental death is associated with loneliness in adulthood, suggesting the need for early intervention in affected children to prevent long-term adverse neuropsychiatric effects.