Importance: Lowering sodium intake reduces blood pressure and may reduce the risk of cardiovascular diseases. The use of reduced-sodium salt (a salt substitute) may achieve sodium reduction, but its effectiveness may be associated with the context of its use. Objective: To identify factors associated with the use of salt substitutes in rural populations in China within the Salt Substitute and Stroke Study, a large-scale cluster randomized trial. Design, Setting, and Participants: This sequential mixed-methods qualitative evaluation, conducted from July 2 to August 28, 2018, in rural communities across 3 provinces in China, included a quantitative survey, collection of 24-hour urine samples, and face-to-face interviews. A random subsample of trial participants, selected from the 3 provinces, completed the quantitative survey (n = 1170) and provided urine samples (n = 1025). Interview respondents were purposively selected from the intervention group based on their different ranges of urinary sodium excretion levels. Statistical analysis was performed from September 18, 2018, to February 22, 2019. Exposures: The intervention group of the Salt Substitute and Stroke Study was provided with the free salt substitute while the control group continued to use regular salt. Main Outcomes and Measures: Knowledge, attitudes, and behaviors regarding the use of the salt substitute were measured using quantitative surveys, and urinary sodium levels were measured using 24-hour urine samples. Contextual factors were explored through semistructured interviews and integrated findings from surveys and interviews. Results: A total of 1170 individuals participated in the quantitative survey. Among the 1025 participants with successful urine samples, the mean (SD) age was 67.4 (7.5) years, and 502 (49.0%) were female. The estimated salt intake of participants who believed that high salt intake was good for health was higher; however, it was not significantly different (0.84 g/d [95% CI, -0.04 to 1.72 g/d]) from those who believed that high salt intake was bad for health. Thirty individuals participated in the qualitative interviews (18 women [60.0%]; mean [SD] age, 70.3 [6.0] years). Quantitative and qualitative data indicated high acceptability of and adherence to the salt substitute. Contextual factors negatively associated with the use of the salt substitute included a lack of knowledge about the benefits associated with salt reduction and consumption of high-sodium pickled foods. In addition, reduced antihypertensive medication was reported by a few participants using the salt substitute. Conclusions and Relevance: This study suggests that lack of comprehensive understanding of sodium reduction and salt substitutes and habitual consumption of high-sodium foods (such as pickled foods) were the main barriers to the use of salt substitutes to reduce sodium intake. These factors should be considered in future population-based, sodium-reduction interventions.